Aim To study the inhibitory effect of ex-opolysaccharide from Rhizopus nigricans ( EPS) combined with oxaliplatin on colon cancer in rats and its mechanism. Methods Colon cancer model in rats was established by subcutaneous injection of 1,2-dime-thylhydrazine ( DMH). The experimental rats were randomly divided into five groups: Control group, model group, EPS group (150 mg • kg-1 ) , oxaliplatin group (10 mg • kg-1 ) and EPS + oxaliplatin group. The his-topathological changes of colon tissues in rats were observed by HE staining. The expression levels of Sur-vivin, caspase-3 and caspase-7 proteins in colon tissues were detected by Western blot and immunohisto-chemistry. Results HE staining results showed that the damage degree of colon tissues could be significantly improved in treatment groups. Compared with model group, the expression of Survivin protein in treatment groups decreased significantly, and the expression of caspase-3 and caspase-7 proteins increased ( P < 0. 05). Conclusions Both EPS and oxaliplatin inhibit colon cancer in rats, and the synergistic effect is more remarkable. Its mechanism may be through inhibiting the expression of Survivin protein and increasing the expression of caspase-3 and caspase-7 proteins, thereby promoting the apoptosis of tumor cells and inhibiting the occurrence and development of tumors.