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Background. Hepatitis B infection can lead to advanced liver disease (ALD) which causes serious health problems. Several factors that are thought to play a role in advanced liver disease are P53, Transforming Growth Factor-β1 (TGF-β1), and Interleukin-10 (IL-10). Therefore, this study aimed to determine the association between P53, TGF-β1, and IL-10 serum levels with ALD.Methods. We collected 68 sera from patients with HBV infection. P53, TGF-β1, and IL-10 serum levels were measured by ELISA. We also detected SNPs from P53 and TGF-b1 genes to determines their associations.Results and Conclusions: In this study, we obtained 41.18% CH patients and 58.82% ALD patients. Male patients outnumbered female in all groups. There was a significant relationship between serum P53 and TGF-b1 levels with ALD (p = 0.03 and 0.01, respectively), but not serum IL-10 levels. However, there was no significant relationship between SNP gene P53 and serum P53 levels nor between SNP gene TGF-b1 and serum TGF-b1 levels (p = 0.73 and 0.23, respectively).Both P53 and TGF-b1 serum leveles can act as biomarkers of prognosis and target therapy for ALD patients.