Objective: To explore the mechanism of mir-873-5p for regulating the proliferation, migration and invasion of colorectal cancer cells. Methods: The colorectal cancer tissue and adjacent normal tissue of 36 patients with colorectal cancer were randomly selected. The expression levels of miR-873-5p and ZEB1 in colorectal cancer tissue and adjacent normal tissue were determined. Methods: human colorectal cancer cell line SW480 was cultured and transfected. The expression levels of mir-873-5p and ZEB1 in the mir-873-5p low-expression group and the control group were determined. The cells were divided into a control group, a mir-873-5p low-expression group and a mir-873-5p + ZEB1 low-expression group, with five wells in each group. Cell proliferation, invasion and migration, and the expression levels of vimentin, ZO-1, E-cadherin, beta - Catenin, N-cadherin and ZEB1 were measured. Results: Compared with adjacent normal tissue, the expression of mir-873-5p was significantly lower and ZEB1 was significantly higher in colorectal cancer tissues (P<0.01). Compared with the control group, the mir-873-5p low-expression group was significantly lower and the ZEB1 expression level was significantly higher (P<0.01). Compared with the control group, the expression level of ZEB1 in the ZEB1 low-expression group was significantly lower (P<0.05). Compared with the control group, the mir-873-5p low-expression group significantly enhanced cell proliferation, colony formation, invasion and migration, and significantly increased the expression levels of vimentin, N-cadherin and ZEB1, and significantly decreased the expression levels of ZO-1, E-cadherin and beta - Catenin (P<0.05); compared with the mir-873-5p low-expression group, the mir-873-5p + ZEB1 low-expression group significantly increased cell proliferation and colony formation. The expression levels of vimentin, N-cadherin and ZEB1 were significantly decreased, and the expression levels of ZO-1, E-cadherin and beta - Catenin were significantly increased (P<0.05). Conclusion: Inhibiting the expression of mir-873-5p can significantly inhibit the proliferation, invasion and migration of colorectal cancer cells and regulate the progress of EMT, which may be achieved by targeting ZEB1.