In order to find new anticancer drugs, a series of novel furoxan-based coumarin derivatives (10a-k) were synthesized and evaluated for their antiproliferative activities in vitro. All compounds displayed more potent inhibition on human cervical cancer HeLa cell proliferation than coumarin-3-carboxylic acid, and compounds 10b, 10c, 10f, 10h, and 10i with IC₅₀ values ranging from 0.88 to 5.95 μM were even stronger than doxorubicin (IC₅₀ = 10.21 μM). The further study showed that compound 10i exerted the highest antiproliferative activity (IC₅₀ = 0.60 μM) against human breast cancer MCF-7 cells, and compound 10f had broader spectrum antiproliferative activity against five cancer cells with IC₅₀ values in the low micromolar range of 1.86-9.85 μM. More interestingly, compound 10f had little effect on normal intestinal epithelial CCD841 cells. Our findings suggest that these novel furoxan-based coumarin derivatives may provide a new framework for the discovery of novel antitumor agents for the intervention of human carcinoma cells.