TThis study aimed to examine the relationship between hepatocellular carcinoma (HCC) susceptibility and two single nucleotide polymorphisms (SNPs) of PNPLA3: rs738409 C > G and rs3747207 G > A. An investigation was carried out on a case-control group of 47 patients with hepatocellular carcinoma (HCC)—20 females and 27 males—with a mean age of 60.62 ± 8.06 years. The control group was made up of 47 volunteers who were in good health and had unrelated, healthy blood donors. They do not suffer from any long-term illnesses and are often recruited. based on the Hardy-Weinberg equilibrium standards. In patients with HCC, the frequency of PNPLA3 rs738409C/G polymorphism was determined to be 23 (48.9%) CC, 22 (46.8%) CG, and 2 (4.3%) GC; in contrast, the control group had 22 (46.8%) CC, 21 (44.7%) CG, and 4 (8.5%) GG [P<0.05]. No statistically significant association was discovered between the PNPLA3 rs738409C/G allele or genotype frequency with the risk of HCC. In contrast, the genotype frequencies of PNPLA3 rs738407A/G I148M in the HCC group were 8 (17.0%) GG, 30 (63.81%) GA, and 9 (19.1%) AA, while control group consisted of 20 (42.6%) GG, 25 (53.2%) GA, and 2 (4.3%) AA. In the total samples, there was a statistically significant positive connection between the risk of HCC and the AA genotype and the A allele. In conclusion, our study suggested that the PNPLA3 rs738407 (GG) genotype and A allele were risk factors for HCC patients.