Objective This study is aimed to verify whether vitexin can increase the sensitivity of colorectal cancer cells to chemotherapeutic drugs. Methods The cell-counting-kit-8 was applied to test the cell viability of HT29 cells. After HT29 cells being co-treated with vitexin and oxaliplatin, western blot was used to check the expression of P-gp, Bax, and Bcl-2 in these groups. The flowcytometry was employed to test the apoptosis rate and cell cycle of HT29 cells after being co-treated with vitexin and oxaliplatin. Results The viability of HT29 cells was decreased gradually via treated with vitexin at the concentration gradients of 30μmol, 60μmol, 90μmol and 120μmol. Western blot showed that compared to the single drug treated group, the relative expression of P-gp and BCL-2 was declined, the expression of Bax was increased in co-treated group. The flow cycometry showed that the G1 phase was significantly expanded and the apoptosis rate of Co-treated group was increased compared to the oxaliplatin single treated group(P<0.05). Conclusion The combination use of vitexin and oxaliplatin can increase the apoptosis of HT29 cells and further increase its sensitivity to the chemotherapeutic drug oxaliplatin.