【Objective】To study the association between the polymorphisms in the promoter region of Osteopontin（OPN）with hepatitis B virus（HBV）-related HCC. 【Methods】A total of 225 cases diagnosed with hepatitis B virus（HBV）-related HCC and 200 age-matched patients with HBV infection without HCC were collected. Three polymorphisms（-156delG/G，-443T/C and -616T/ G）in the Osteopontin promoter were genotyped using direct sequencing.【Results】The frequency of -156delG/delG genotype in the HCC group was higher than that of in the control group（P = 0.003）. There was a significantly increased frequency of the allele -156delG（P < 0.001）in HCC patients. Logistic regression analysis was performed to show an increase HCC risk associated with the delG variant genotype（OR1.64；95%CI 1.25 ~ 2.16）. There were no differences between the groups in the genotype distributions and allele frequencies of SNP -443T/C and -616T/G. 【Conclusion】Our findings suggest that allele -156delG in the Osteopontin promoter may be a marker for risk of HCC with HBV infection in Chinese Han population.