Objective: To investigate the inhibitory effect of caffeic acid phenethyl ester (CAPE) on human colon cancer HT-29 cells and its influence on the c-Jun N-terminal kinase (JNK) signaling complex. Methods: The human colon cancer HT-29 cells were cultured in vitro, and then the inhibition rate of cell growth was measured by MTT assay after the HT-29 cells were exposed to different concentrations of CAPE over different time periods. Next, the expression levels of JNK and paxillin protein in HT-29 cells were detected by Western blot analysis after 24 h exposure to different concentrations of CAPE. Results: All the 4 concentrations (2.5, 5.0, 7.5 and 10.0 μg/L) of CAPE inhibited the proliferation of HT-29 cells, which showed a concentration- and time-dependent effect (all P<0.01). All the 4 concentrations of CAPE decreased the expression levels of JNK and paxillin protein, which showed a concentration-dependent effect (all P<0.01). Conclusion: CAPE can inhibit the proliferation of human colon cancer HT-29 cells in vitro, and the mechanism may be related to its reducing the activity of JNK-paxillin signaling pathway.