Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the major risk factors include chronic infections with the hepatitis B or C virus, and exposure to dietary aflatoxin B1 or alcohol consumption. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC. Heat shock proteins have essential roles in protecting cells from the potentially lethal effects of stress. They have dual roles as a modifier to protein activities and as a central regulator in both cell proliferation and apoptosis. Among them, HSP70 are often overexpressed in cells of various cancers and have been suggested to contribute to tumorigenesis. 50 patients with liver disease were enrolled in this study compared to 10 healthy volunteers, matched for age and sex, served as the control group. The studied patients were divided into 2 groups; Group I: those suffering from HCC and Group II: those suffering from post hepatitis B and C liver cirrhosis. Diagnosis of the studied groups was based on compatible clinical and ultrasonographic findings, serum AFP levels .The presence of p53gene mutation was detected by DNA extraction from whole blood from patients and controls followed by polymerase chain reaction then restriction fragment length polymorphism (RFLP) analysis of codon 249 of exon7. Our result revealed that in group II (liver cirrhosis) and control group; no point mutation at codon 249 of exon7 could be detected, while in the HCC group: out of 20 patients 3/20 (15%) showed point mutation at codon 249 of exon7. There was no statistical significant difference between Group I (HCC), Group II(liver cirrhosis) and control group as regard exon7 mutation of p53 gene (P>0.05).Also we examine HSP70 genes polymorphism by the same technique PCR-RFLP. HSP70-1genotype In Group I (HCC): b1/b1and b2/b2 was 5% and 95%. In Group II: b1/b1and b2/b2 was 20% and 80%. In the control Group: b1/b1and b2/b2 was 0% and 100% respectively. HSP70-2 genotype A/A, A/B and B/B .In Group I (HCC): was 0%, 25% and 75%.In Group II: was 10%, 20% and 70%.In the control Group: was 0%, 50% and 50% respectively.