Abstract: OBJECTIVE To investigate the influence of quercetin on the apoptosis of human colon cancer HT-29 cells in vitro and study the induced mechanism. METHODS Human colon cancer HT-29 cells were cultured in vitro and divided into 4 groups, including control group, high-dose quercetin group (32 μg·mL^-1), medium-dose quercetin group (316 μg·mL^-1) and low-dose quercetin group (8 μg·mL^-1). After quercetin intervention for 24 h, CCK-8 kit was used to observe the effect of quercetin on HT-29 cells proliferation; alterations of HT-29 cells morphology were determined using inverted microscope; Western blot technology was used to detect the expression levels of MKK3/6, p38, p-MKK3/6, p-p38, Caspase 8, Caspase 3, Bax and Bcl-2. RESULTS These findings showed that quercetin could significantly inhibite the proliferation of HT-29 cells in vitro; HT-29 cells density significantly decreased and cells size significantly lessened after quercetin intervention for 24 h; moreover, the phosphorylation levels of MKK3/6 and p38 were significantly rised induced by quercetin, and pro-apoptotic protein (Caspase8, Caspase3, Bax) significantly up-regulated while anti-apoptotic protein (Bcl-2) significantly inhibited by quercetin. CONCLUSION Quercetin can induce the apoptosis of human colon cancer HT-29 cells and the mechanism may relate to the activation of MKK3/6/p38 signal pathway.