Human HCC is among the most frequent worldwide malignancies. However, no effective therapy has existed as of yet. The purpose of this study is to look into the molecular evaluation of the p53 Arg72Pro and hTERT rs2736098 polymorphisms in hepatocellular carcinoma. The study was conducted in 70 untreated known cases of HCC and 40 healthy controls. The levels of alfa fetoprotein (AFP) were tests for all samples to detect the early stages of HCC. Triphasic CT was abdomen for patients with HCC to determine the stages of HCC. All samples were tests for biochemical and hematological parameters as liver functions tests. Genotyping of hTERT and p53 gene was done by PCR-Restricted fragment length polymorphism-PCR (PCR-RFLP). P53 Arg72Pro distributions showed that there are statistically significant differences between HCC and the control group in either genotype (Arg/Arg) or allele (G) distribution. Moreover, a significant association was found between HCC and the control group regarding hTERT rs2736098 (GG) genotype and (G) allele. No statistically significant correlation was detected between the studied polymorphisms and the clinicopathologic markers or SNPs stratification based on HCV carrier in HCC groups. In Conclusion: There is an association of p53 codon 72 polymorphism and hTERT polymorphism (rs2736098) with risk of hepatocellular carcinoma in Egyptian patients, which could be used as a potential non-invasive biomarker to attain early diagnosis of HCC.