Abstract Infection with the hepatitis B virus (HBV) continues to be a hazard for public health across the globe. Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are all possible outcomes (HCC). It is obvious that certain patients with chronic hepatitis B (CHB) viral infection developed HCC, while other under almost similar circumstances do not. To inspect the possible there being a link between three single nucleotide gene polymorphisms (SNPs) in GzmB genes with the development of HCC. A total of 85 patients diagnosed with CHB participated in this research (40 patients with HCC and 45 patients without HCC). Three SNPs in GzmB gene (rs7144366, rs8192917 and rs2236338) were genotypes using restriction fragment length polymorphism (RFLP). The haplotype blocks derived from the three SNPs were assembled, and the linkage disequilibrium (LD) between the SNPs was determined using the SHEsis software. The homozygous mutant genotype (CC) was shown to be significantly more common in patients with HCC (27.5 %) than in those without HCC (11.11 %) (OR= 3.93, 95 percent CI=1.13-13.62, p=0.031). At allelic level, the mutant allele (C) was more frequent in patients with than those without HCC (46.25% vs. 26.67%) with a significant deviation (OR=2.36, 95%CI= 1.25- 4.49, p= 0.008). the haplotype block CCG was more common among patients with HCC (26.25%) than those without HCC (12.22%) with a significant difference (OR= 2.56, 95%= 1.14-5.71, p= 0.022). the final conclusion carrying the mutant homozygous (CC) of the SNP rs8192917 and allele C of this SNP may have a higher chance of developing HCC compared with those carrying other genotypes and T allele of the SNP. The haplotype block CCG (corresponding for TC allele of rs7144366, C allele of rs8192917 and G allele of rs2236338) might be regarded as a risk factor for the emergence of HCC in patients with CHB.