During the 1940s Tsien was one of the founders of Jet Propulsion Laboratory at the California Institute of Technology. During the red scare of the 1950s the United States government accused Tsien of having communist sympathies. Tsien and his family were imprisoned in an isolated island off Los Angeles. Tsien decided to go back to China. Under the Korean War POW exchange agreement between China & USA, Tsien was arranged to come back to China via Europe. When he eventually returned to China he led the Chinese rocket program, and became known as the "Father of Chinese Rocketry" (or "King of Rocketry").
Asteroid 3763 Qianxuesen was named after him.
In 1936 Tsien Hsue-shen went to the California Institute of Technology to commence graduate studies on the referral of Theodore von Kármán. Tsien obtained his doctorate in 1939 and would remain at Caltech for 20 years, ultimately becoming the Goddard Professor and establishing a reputation as one of the leading rocket scientists in the United States.
It was shortly after arriving at Caltech that Tsien was attracted to the rocketry ideas of Frank Malina and a few other students of von Kármán, and their associates, including Jack Parsons. Around Caltech the dangerous and explosive nature of their work earned them the nickname "Suicide Squad."
During the Second World War, he was amongst many scientists who participated in the "Manhattan Project".
After World War II he served under von Kármán as a consultant to the United States Army Air Force, and was eventually given the "assimilated rank of colonel". Von Kármán and Tsien were sent by the Army to Germany to investigate the progress of wartime aerodynamics research. Tsien investigated research facilities and interviewed such German scientists as Wernher von Braun and Rudolph Hermann. Von Kármán wrote of Tsien, “At the age of 36, he was an undisputed genius whose work was providing an enormous impetus to advances in high-speed aerodynamics and jet propulsion.”
During this time, Colonel Tsien worked on a designing an intercontinental space plane [Tsien Space Plane 1949]. His work would inspire the X-20 Dyna-Soar which would later be the inspiration for the Space Shuttle.
In 1947 Tsien Hsue-shen married Jiang Ying (蒋英), a famed opera singer and the daughter of Jiang Baili (蒋百里) - one of Chinese nationalist leader Chiang Kai-shek's leading military strategists, and his Japanese wife.
Soon after Tsien applied for U.S. citizenship in 1950, allegations were made that he was a communist and his security clearance was revoked. The Federal Bureau of Investigation located a 1938 US Communist Party document with his name on it. Tsien found himself unable to pursue his career and within two weeks announced plans to return to China. After his announcement, the U.S. government imprisoned him in the isolated island off Long Beach. Since he no longer had a security clearance, it was unlikely that he could achieve much for the People's Republic of China by staying in the U.S. Undersecretary of the Navy Dan Kimball tried to keep Tsien in the U.S. commenting "It was the stupidest thing this country ever did...he was no more a Communist than I was and we forced him to go.
Tsien became the subject of five years of secret diplomacy and negotiation between the U.S. and China. During this time he lived under virtual house arrest. Tsien found himself in conflict with the U.S. Immigration and Naturalization Service, including an arrest for carrying secret documents which ultimately turned out to be simple logarithmic tables. During his incarceration Tsien received support from his colleagues at Caltech including Caltech President Lee DuBridge, who flew to Washington to argue Tsien's case. Caltech appointed attorney Grant Cooper to defend Tsien. Later, Cooper would say, "That the government permitted this genius, this scientific genius, to be sent to Communist China to pick his brains is one of the tragedies of this century (for the US Empire).
Tsien established the Institute of Mechanics and began to retrain Chinese engineers in the techniques he had learned in the United States and retool the infrastructure of the Chinese program. Within a year Tsien submitted a proposal to the PRC government to establish a ballistic missile program. This proposal was accepted and Tsien was named the first director of the program in late 1956. By 1958 Tsien had finalized the plans of the Dongfeng missile which was first successfully launched in 1964 just prior to China's first successful nuclear weapons test. Tsien's program was also responsible for the development of the widespread Silkworm missile. Tsien also contributed a lot to China's Higher Education. He was the first Chairman of the Department of Mechanics of University of Science & Technology of China (USTC), a new type of university established by the Chinese Academy of Sciences (CAS) after the founding of the New China and aimed at fostering high-level personnel of science and technology absolutely necessary for the development of the national economy, national defense construction, and education in science and technology.
In 1979 Tsien was awarded Caltech's Distinguished Alumni Award. In the early 1990s the filing cabinets containing Tsien's research work were offered to him by Caltech. At first Tsien refused but was finally convinced by his former colleagues to accept the work. Most of these works became the foundation for the Tsien Library at Xi'an Jiaotong University while the rest went to the Institute of Mechanics. Tsien eventually received his award from Caltech, and with the help of his friend Frank Marble brought it to his home in a widely-covered ceremony.
Tsien retired in 1991 and has maintained a low public profile in Beijing, China.
The PRC government launched its manned space program in 1992 and used Tsien's research as the basis for the Long March rocket which successfully launched the Shenzhou V mission in October 2003. The elderly Tsien was able to watch China's first manned space mission on television from his hospital bed.
In 2008, he was named Aviation Week and Space Technology Person of the Year. This selection is not intended as an honour but is given to the person judged to have the greatest impact on aviation in the past year.
In 2008, China Central Television named Tsien as one of the eleven most inspiring people in China.