ABSTRACT In this present study, we try to investigate the hepatotoxicity effect of RIF and INH vis chlorinative stress pathway in vitro, by measured catalase (CAT) kinetic parameters and Advanced Oxidation Protein Products (AOPPs) level. In this experiment, a liver sample was taken from male rats (Rattus novergicus). Sample the homogenized and divided into three groups with; T0 served as control which contains liver, T1 which contains liver homogenate + 450 mg Rifampicin (RIF); and T2 which contains liver + 300 mg Isoniazid (INH). For CAT kinetic parameters analysis (Km, Vmax, and kcat), in each solution was added hydrogen peroxide (H2O2) with different concentrations. Solutions then incubated at 37oC for 1 hours and then was prepared for kinetic parameter analysis. The AOPPs level was analysed using spectrophotometric methods. The results showed that both RIF and INH treatments could decrease the affinity of H2O2-CAT complex and increase the turnover rate of the reaction which expressed by the higher Km, Vmax, and kcat values. Also, the results showed that both RIF and INH significantly increased the level of AOPPs in liver homogenate. From this results, it can be concluded that both RIF and INH-induced hepatotoxicity via chlorinative stress pathway by disrupting the CAT activity and increased the AOPPs level.