In 1933 Strassmann resigned from the Society of German Chemists when it became part of a Nazi-controlled public corporation. He was blacklisted by the Nazi regime. As a result, he could not work in the chemical industry nor could he receive his habilitation as required to be an independent researcher in Germany at the time. Lise Meitner encouraged Otto Hahn to find an assistantship for Strassmann at half pay, and he eventually became a special assistant to Meitner and Hahn. Strassmann considered himself fortunate, for "despite my affinity for chemistry, I value my personal freedom so highly that to preserve it I would break stones for a living."
Strassman's wife Maria supported his refusal to join the Nazi Party.  During World War II they concealed a Jewish woman, musician Andrea Wolfenstein, in their apartment for months, putting themselves and their three-year-old son at risk. Strassmann continued his research in radiochemistry during World War II, although he did not work on weapons development. He disdained the Nazi regime and is reported to have said, "If my work would lead to Hitler having an atomic bomb I would kill myself."