Abstract Hepatocellular carcinoma (HCC) is commonly known as”the king of cancer”, with high mortality and low survival due to advanced stage and poor clinical outcomes worldwide. Development of HCC is a multistep process which involves in genetic factors such as alterations of oncogenes and tumor suppressor genes, and environmental exposure like viral infections and aflatoxin contamination as well. The p53 tumor suppressor protein plays key roles in tumor development and progression, and single nucleotide polymorphism (SNP) of the p53 gene codon 72 (P53Arg/Pro) changes the structure of the protein and affects its activity which might affect cancer risk. Data showed that the prevalence of P53Arg/Pro different genotypes varied with race and geographic location, and previous studies provided controversial findings about the association of P53Arg/Pro and HCC incidences. A case-control study here was employed to investigate the associations between p53 codon72 polymorphism and HCC susceptibility in Chinese population of northeast Sichuan. A total of 150 subjects with HCC and 341 cancer-free control subjects were involved in this study. Genomic DNA was extracted from peripheral blood and the p53 codon72 polymorphism was measured by Taqman MGB, a fluorescent quantitative real time PCR assay. The distribution frequency of p53 sites was compared between the HCC group and the control, including the stratified and interaction analysis of the related environmental factors about HCC in order to understand the roles of p53 codon72 polymorphism and environmental factors in the development of HCC. The results showed that the distribution frequency of p53 sites of Arg/Arg, Arg/Pro, Pro/Pro were 18.0%, 48.7%, 33.3% in HCC group,and 16.4%, 47.8%, 35.8% in the control respectively, which indicated that there was no obvious differences between the two groups. Further stratified with smoking, alcohol drinking, gender, HBV infection,no risk increasing genotype was found either. However, interactions between p53 codon72 polymorphism and above environmental conditions exposure might increase the risk of HCC(smoking OR = 2.18,95%CI:1.12-4.25), (gender OR = 3.01,95%CI:1.00-9.14), (HBV infection OR = 6.05,95%CI:2.29-16.00), respectively. Our findings indicated that no significant association was found between p53 codon72 polymorphism and the susceptibility to HCC in Chinese population of Northeast Sichuan currently.; However, interaction between genetic factors and environment exposure significantly increased the risk of HCC. This study suggests some environmental exposure control measures, such as smoking cessation, hepatitis B vaccination and early screening for men at high-risk age, which could be taken to effectively prevent the development of HCC. Citation Format: Jiajing Cai, Yan Cai, Qiang Ma, Dongsheng Wang, Guoyuan Zhang, Xiaolan Guo. Association of p53 codon72 polymorphism with susceptibility to hepatocellular carcinoma in Chinese population of Northeast Sichuan. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1226. doi:10.1158/1538-7445.AM2015-1226