Background: examining the alteration of cell cycle genes in early hepatitis C virus (HCV) found that altered expression of mitotic checkpoint genes, MAD2L1, KNTC1, CDC16 and CDC34, KNTC1 known as “rough deal protein" (ROD) is part of a complex involved in elaborating an inhibitory signal due to improper chromosomal aligment during cell division. Aim of the work: attempt for the identification of proteins (genes), which act as predictive factors to identify patients with high risk of cell transformation and HCC development. Patients and methods: fifty three patients with chronic HCV infection, age ranged between 18 and 58 years, time of assessment was before starting therapy of hepatitis C at the National Hepatology and Tropical Medicine Research Institute. Ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography, and collection of blood samples for routine laboratory investigation; CBCs. Liver biopsy was done to all patients and controls, patients revealed mild fibrosis (Metavir fibrosis scores from F1 to F3).  Also, we used freshly frozen liver biopsies mRNA levels with perspective protein levels of four genes:  P27, P15, KNTC1, MAD2L1. Results: significant association of P27, P15, KNTC1 and MAD2L-1 with the progression of liver fibrosis in chronic HCV liver biopsy was found. Conclusion: there is altered gene expression in HCV-associated liver disease. Recommendations: the emerging interest of hepatologists in the influence of genetic factors in HCV. Evaluation of the expression of key proteins related to the cell cycle and apoptosis in chronically infected patients with HCV would be of significance to understand disease pathogenesis, and will help in identifying novel prognostic indicators.