Objective:To investigate the possible association between codon 2020 polymorphism(Asn2020Ser) of IGF2R gene and the susceptibility to colorectal cancer(CRC) and hepatocellular carcinoma(HCC) in Chinese population. Methods: The IGF2R Asn2020Ser genotypes were determined by TaqMan assay in 345 CRC cases and 670 controls,and in 469 HCC cases and 558 controls. Odds ratios(OR) for cancer and 95% confidence intervals(CI) from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and cancer risk. Results: The Ser allele of the IGF2R Asn2020Ser polymorphism was significantly associated with decreased risks of CRC and HCC. As compared with Asn/Asn genotype,Asn/Ser,Ser/Ser and Ser-allele carriers(Asn/Ser or Ser/Ser genotype) had significantly decreased risks of CRC,with the decrease being 0.71-fold (95% CI=0.54-0.94,P=0.017),0.64-fold(95% CI=0.42-0.97,P=0.036) and 0.69-fold(95% CI=0.53-0.90,P=0.008),respectively. A similar decreased HCC risk was also shown,with the decrease being 0.68-fold(95% CI=0.52-0.89,P=0.005) for Asn/Ser genotype,0.78-fold(95% CI=0.52-1.16,P=0.212) for Ser/Ser genotype,and 0.70-fold(95% CI=0.54-0.90,P=0.006) for Ser-allele carriers,when compared with Asn/Asn genotype. Conclusion: The Ser allele of the IGF2R Asn2020Ser polymorphism is potentially one of the protective factors against CRC and HCC in Chinese population.