Background: Colon carcinoma growth depends on many factors such as, different organisms, and immune cells, which induce and produce inflammatory cytokines. UMBELLIPRENIN is a naturally prenylated coumarin with anti-inflammatory activities. Its ability to induce cancer cell death has shown variation on different cancer cell lines.Objectives: 7-Prenyloxycoumarins, including UMBELLIPRENIN have been widely investigated because of their pharmacological activities. This paper shows the effect of UMBELLIPRENIN on colon cancer cell lines.Material and Methods: In the present study, invasive SW48 and noninvasive SW1116 were treated with UMBELLIPRENIN (6.25, 12.5, 25, 50, 100, and 200 mM), and the cytotoxicity was determined using a methyl thiazolelydiphenyl-tetrazolium bromide (MTT) assay.Results: UMBELLIPRENIN had significant cytotoxic activity against SW48 cells at all study concentrations (except for 6.25 mM), with IC50 values of 117, 77, and 69 mM after 24, 48, and 72 h, respectively. However, it was cytotoxic against SW1116 only at higher concentrations of 100 and 200 mM (34% and 64% cell death). At lower concentrations, UMBELLIPRENIN showed a significant proliferative effect on this noninvasive cancer cell line. Our data were validated by eye and microscopic images.Conclusions: We found a moderate cytotoxic activity of UMBELLIPRENIN against invasive SW48 cells, and both cytotoxic and proliferative effects on noninvasive SW1116 cells. Therefore, using UMBELLIPRENIN as an anti-inflammatory or cytotoxic compound for patients with colon cancer should be used with care.