Our previous study has reported that interleukin-16 (IL-16) genetic polymorphisms are significantly related to chronic hepatitis B (CHB) and hepatitis B virus-related (HBV-related) hepatocellular carcinoma (HCC). As CHB, liver cirrhosis (LC), and HCC are development processes, this study aimed to determine genetic correlation of IL-16 polymorphisms with HBV-related LC in a Chinese population. IL-16 gene rs11556218, rs4072111, and rs4778889 polymorphism in 129 patients with HBV-related LC and 168 healthy individuals were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PCR-RFLP results were verified by DNA sequencing. The allelic and genotypic distributions of IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms in HBV-related LC patients showed no significant difference from those in healthy controls. Furthermore, no relationship was observed between the haplotype distribution and susceptibility to HBV-related LC. This work provided the first evidence that the IL-16 genetic polymorphisms may not be associated with HBV-related LC risk.