Background: human immune deficiency virus (HIV) infection is a public health concern inrndeveloping countries. Non-AIDS causes of morbidity and mortality are becoming increasingly rncommon in patients chronically infected with HIV. In particular, liver-related diseases havernrisen to become one of the leading causes of non AIDS-related death. rnObjective: This study was intended to assess the magnitude, severity and determinants ofrnhepatotoxicity in HIV infected patients taking Dolutegravir (DTG) based and Efavirenze (EFV) rnbased HAART regimen in ACSH, Mekelle, Ethiopia, 2020. rnMethods: Institutional based cross-sectional study was conducted using convenient and quotarnsampling method to assess the prevalence, magnitude and determinants of hepatotoxicity among rnthe study participants in ACSH, Ethiopia from December â€“December 2020. SPSS version 25.0rnwas used for analysis. Data on socio-demographic as well as clinical characteristics of 224rnstudy participants were assessed. Structured questioner, anthropometric measurements, medicalrnrecords and smart care were used to obtain the data. Becton Dickinsonâ€™s (BD) FACS caliberrnflow cytometer, Chemistry analyzer machine (Mindray BS-200) and HCV &HBV test strips werernused to determine CD4 count, liver function biomarkers, and HBV or HCV infections. rnResults: The overall prevalence of hepatotoxicity were found to be 33.9% (n=224) in bothrnstudy groups. The prevalence of hepatotoxicity was higher among those on Dolutegravir (DTG) rnbased regimen 41.1% (n=112) as compared with those who took Efavirenze (EFV) basedrnregimen 26.8% (n=112) (P=0.024). Multi variate analysis in patients on DTG containingrnHAART regimen showed that CD4 count of 12 months), poor adherence to HAART, having addiction habit and BMI of