Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) reportedly plays a crucial role in tissue inflammation and tumourigenesis. Our previous studies have demonstrated that PIN1 gene polymorphisms are significantly related to the pathogenesis of hepatitis B virus (HBV)-related liver cancer in a Guangxi population. As chronic hepatitis B (CHB), liver cirrhosis (LC), and liver cancer are development processes, we further investigated whether any relationship exists between PIN1 gene polymorphisms and the risk of CHB and HBV-related LC. We used the polymerase chain reaction restriction fragment length polymorphism and the deoxyribonucleic acid sequencing method to analyze 3 common single-nucleotide polymorphisms (SNPs) (rs2233678, rs2233679, and rs2233682) of the PIN1 gene in 192 CHB patients, 171 HBV-related LC patients, and 201 healthy controls in this research. The results revealed that carriers of the rs2233682 A allele had a significantly decreased risk of HBV-related LC (LC vs. controls: odds ratio [OR] = 0.262, 95% confidence interval [CI] = 0.071-0.959, P = .043; LC vs. CHB: OR = 0.198, 95% CI = 0.049-0.803, P = .023). Similar relationships were observed for the PIN1 rs2233682 GA genotype among the groups (LC vs. controls: OR = 0.248, 95% CI = 0.067-0.919, P = .037; LC vs. CHB: OR = 0.184, 95% CI = 0.044-0.773, P = .021). This reduced risk was more obvious in older CHB patients (age ≥50 years). No such correlations were found for PIN1 rs2233678 and rs2233679. However, the haplotypes constructed from these SNP (GCA for controls and CCG for CHB) were associated with a significantly decreased risk of HBV-related LC. In summary, the findings of this study suggest that the PIN1 rs2233682 A allele might be related with a decreased risk of HBV-related LC in a Guangxi population.