Mutations in the-p53 gene are frequent genetic alteration in human hepatocellular carcinoma (HCC). In the present study, we examined 30 HCC cases from the in-patient section in the National Liver Institute, Menouflya University, also 20 apparently healthy individuals, of matched age and sex, were taken as a control group. Twenty-three cases out of 30(76.7%) were seropositive for HCV, 9 oases (30%) were seropositive for HBV and 7 cases (23.3%) towed seropositivity for both HCV and HBV. The presence of p53 alterations was detected by DNA extraction from fresh frozen section of tumors and whole blood from patients and controls, followed by polymerase chain reaction then restriction fragment polymorphism analysis of exon 4 and exon 7 respectively. u]t showed that 13 cases (43.3%) had loss of heterozygosity at codon 72 of exon 4, while 4 cases (13.3%) showed p53 mutation at codon 249 of exon 7. There is a significant correlation between hepatitis infections and p53 aberration. It is concluded was a low inci4ence of p53 mutation at codon 249 of 7 of 11CC, also it was noticed that increase incidence of LOH codon 72 of exon 4 suggestted that both HCV and HBV infections play a role in 11CC carcinogenesis.