〔Abstract〕 Objective To investigate the expression and clinical significance of erbb2 interacting protein(ERBIN) and PDZ domain containing 2 protein(PDZD2) in colorectal cancer tissues, as well as the effects of ERBIN and PDZD2 on the progression of colorectal cancer and the corresponding mechanisms. Methods Western blot was used to detect the expression of ERBIN and PDZD2 proteins in tumor tissues and corresponding adjacent tissues from 86 colorectal cancer patients, as well as normal human colon fibroblasts(CCD-18 Co) and human colorectal cancer cell lines(SW480, HCT116, SW620 and HT29); SW620 and HCT116 cells were transfected with ERBIN or PDZD2 overexpression vector, and then cell proliferation, cell invasion and apoptosis were detected. The expression of ERBIN or PDZD2 protein in SW620 cell was observed by immunofluorescence chemistry. Co-immunoprecipitation assay was used to detect the interaction between ERBIN and PDZD2 proteins. Results The expression levels of ERBIN and PDZD2 proteins in colorectal cancer tissues were lower than those in adjacent tissues(P<0.01), and the expression levels of ERBIN and PDZD2 in colorectal cancer cells were lower than those in CCD-18 Co cells(P<0.01). The expression levels of ERBIN and PDZD2 proteins were correlated with the depth of invasion, differentiation, TNM staging and lymph node metastasis of colorectal cancer(P<0.001); ERBIN or PDZD2 overexpression reduced the proliferation and invasion of SW620 and HCT116 cells(P<0.01), increased cell apoptosis(P<0.01); ERBIN directly bound to PDZD2, and overexpression of ERBIN increased the expression level of PDZD2 protein. Conclusion ERBIN can inhibit the proliferation and invasion of colorectal cancer cells and promote apoptosis by promoting the expression of PDZD2 protein.