In order to find new anti-tumor drugs from natural resources, six of new isopimaric thiophene sulfonamides derivatives (5a~5f) were designed and synthesized. And the structure of the compounds was confirmed. In addition, the cell proliferation inhibition assay (MTT method) was used to study the in vitro inhibitory activity of 5a~5f on four human tumor cells. The results showed that some compounds had good inhibitory activities against four kinds of human tumor cells; at the concentration of 100 μg?mL-1, isopimaric acid acyl- 2-chloropyridine-5-sulfonamide(5d) and isopimaric acid acyl- 3-bromo-2-chloropyridine-5-sulfonamide(5e) exhibited favorable ntitumor activities against cervical cancer (Hela), breast cancer cells (MDA-MB-231), prostate cancer (PC-3) and hepatocarcinoma cells (HepG-2) respectively, which was all over 95% and 90%; Isopimaric acid acyl- 3-chloroquinoline-sulfonamide(5c) has a good inhibitory activity on the above four human tumor cells. The IC50 values of compounds 5d and 5e were lower than those of 5-fluorouracil (5-FU), which was widely used in clinic. It indicated that compounds 5d and 5e had good clinical application prospects.