Objective To explore the effect of receptor interacting protein 2 (RIP2) in invasion and migration of colorectal cancer (CRC), expression of RIP2 in CRC was tested, and variety was observed after RIP2 was inhibited in CRC cell line. Methods Sixty-eight cases of CRC paraffin-embedded specimens and 50 cases of tumor-adjacent tissues were collected, and the expression of RIP2, matrix metalloproteinase (MMP)-2 and MMP-9 was detected by immunohistochemistry (IHC), then clinicopathological parameters of patients were also recorded. The relationship among 3 proteins was also evaluated. RNA interference (RNAi) technology was employed to inhibit the RIP2 in HT29 cells, and variety of invasion and migration was tested in HT29 cells. Results It was showed that positive expressions of RIP2 (67.65%) was higher in CRC tumors than in tumor-adjacent tissues (28.00%) (χ2=4.819, P<0.01). Expression of RIP2 was correlated with tumor invasion depth, lymph node metastasis (χ2=4.390, P<0.05; χ2=5.569, P<0.05). There was positive relationship between RIP2 and MMP-2, RIP2 and MMP-9 (r=0.326, P<0.01; r=0.439, P<0.01). After RIP2 inhibition, migration ability of HT29 cells weakened (F=36.471, P<0.01), and expressions of MMP-2, MMP-9 decreased simultaneously (F=9.090, P<0.05; F=5.732, P<0.05). Conclusion RIP2 was up-regulated in CRC tissues, and RIP2 may promote invasion and metastasis of CRC by regulating MMP-2, MMP-9. Key words: Colorectal cancer; Receptor interacting protein 2; Gene interference; Invasion; Metastasis