Background: Gravity is omnipresent on Earth; however, humans in space, such as astronauts at the International Space Station, experience microgravity. Long-term exposure to microgravity is considered to elicit physiological changes, such as muscle atrophy, in the human body. In addition, certain types of cancer cells demonstrate inhibited proliferation under condition of time-averaged simulated microgravity (taSMG). However, the response of human Hodgkin's lymphoma cancer cells to reduced gravity, and the associated physiological changes in these cells, have not been elucidated. Methods: In this study, the proliferation of human Hodgkin's lymphoma cancer cells (L-540 and HDLM-2) under taSMG condition (<10(-3) G, 1 G is defined as 9.8 m/s(2)) was studied using a 3D clinostat. Normal human dermal fibroblast (HDF) was proliferated in the same condition as a control group. For the development of 3D clinostat, two motors were used to actuate the frames. Electrical wires for power supply and communication were connected via slip ring. For symmetrical path of gravitational vector, optimal angular velocities of the motors were found using simulation results. Under the condition of taSMG implemented by the 3D clinostat, proliferation of the cells was observed for 3 days. Results: The results indicated that proliferation of these cancer cells was significantly (p < 0.0005) inhibited under taSMG, whereas proliferation of normal HDF cells was not affected. Conclusions: Findings in this study could be significantly valuable in developing novel strategies for selective killing of cancer cells such as lymphoma.