Background and purpose: Crocetin is a natural antioxidant that is found in the crocus flower and Gardenia jasminoides (fruit). Previous studies have reported its anticancer activity both in vivo and in vitro . In addition, crocetin suppresses the growth and migration of human colorectal cancer cells, however, its mechanism of action remains to be elucidated. Therefore, the present study investigated the molecular mechanism of crocetin effect on colorectal cancer cells (HCT-116) in vitro . Experimental approach: HCT-116 cells were treated with different concentrations (0, 200, 400, 600, and 800 μM) of crocetin for 24 h. The cell survival rate was measured by MTT assay. Cell migration capacity was evaluated using the wound healing assay. The expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP-9) was monitored by RT-PCR. Phosphorylation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) was determined using western blot. Findings/Results: The proliferation of HCT-116 was inhibited by crocetin at 800 μM ( P < 0.001). Crocetin prevented migration of HCT-116 cells ( P < 0.05) and suppressed VEGF and MMP-9 mRNA expression ( P < 0.001) and increased phosphorylation of p38 (MAPK; P < 0.001). However, no significant change in the phosphorylation of FAK was observed. Conclusion and implication: These data suggested that crocetin-induced growth- and migration- suppressing effects on HCT-116 cells may partially depend on the regulation of the p38 (MAPK) signaling pathway.