Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern, often progressing to hepatocellular carcinoma (HCC), a leading cause of liver cancer. This research investigates the relationship between NAFLD and HCC in HepG2 cells and the roles of p53 and alpha-fetoprotein (AFP) in these processes. The study investigated that the inactivation of p53 (NAFLD = 22.5 ±2.02U/ml, HCC = 55 ±2.21U/ml) contributes to the progression of NAFLD to HCC, and that elevated AFP levels (NAFLD = 13 ±1.17ng/ml, HCC = ±1.2ng/ml) serve as both a biomarker and a contributor to liver carcinogenesis (p-value < 0.5). The findings highlight that the elevated values of AFP, but not of P53, may help in understanding the transformation in the context of NAFLD and liver cancer.