Objective To explore the associations between polymorphisms in CYP24A1 gene and the risk and prognosis of colorectal cancer (CRC).Methods A case-control study consisting of 528 CRC patients and 605 cancer free controls and a follow up study with 317 cases were conducted to explore the associations between two polymorphisms in CYP24A1 and the risk and prognosis of CRC,as well as the combinations and interactions of polymorphisms with dietary factors on CRC risk.Results Although there was no association between polymorphisms in CYP24A1 and the risk of CRC,significant combinative effects between polymorphisms and dietary factors on CRC risk were observed.For Rs4809957 polymorphism,the prognosis of AA genotype carriers was worse than GG/GA carriers in CRC,colon cancer and rectal cancer(Log-rank test P=0.01,P=0.01,P=0.02,respectively).Compared with GG genotype,AA genotype carriers of Rs4809957 polymorphism had worse prognosis in CRC(HR = 2.35,95% CI = 1.28~4.30),colon caner(HR = 2.37,95% CI =1.09~5.14)and rectal cancer(HR = 2.11,95% CI = 1.11~4.01).Conclusion The combinations of the polymorphisms in CYP24A1 gene with dietary factors are associated with the susceptibility of CRC,and Rs4809957 polymorphism may lead to a worse prognosis of CRC.