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To evaluate the microsatellite instability (MSI), expression of mismatch repair (MMR) gene (hMLH1, hMSH2) and proliferation kinetics in colorectal cancer (CRC) with familial predisposition. Method:Forty-six cases of CRC were studied using silver staining polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, streptavidin-peroxidase (SP) immunohistochemical method and flow cytometry. Results: In CRC patients with familial predisposition, the MSI-positive rate was higher than in sporadic CRC (P＜0.05). Familial predisposition and positive MSI were strongly related to early age of cancer onset, the proclivity for proximal colonic cancer, poor differentiated and extracolorectaln malignancies (P＜0.01, P＜0.05). The incidence of negative expression ofhMLH1 in tumor tissue and hMLH1, hMSH2 in normal colorectal tissues was significantly higher (P＜0.05). The negative expression of hMLH1 together with hMSH2 was related with positive MSI (P＜0.05).In MSI-positive CRC cells, the proliferation cell nucleus antigen (PCNA) expression, proliferation index and S-phase cells decreased obviously (P＜0.01, P＜0.05). Conclusion: In CRC with familial predisposition, MSI might be an important contributor. The rate ofhMLH1 and hMSH2 mutation increased in tumor and normal tissue, and the proliferation activity of their cancer cell was lower.