Phyllanthus niruri L. (Euphorbiaceae) is a well-known hepatoprotective herbal plant. The aim of this study was to investigate the hepatoprotective action of the protein isolate of Phyl-lanthus niruri (P. niruri) against acetaminophen (APAP) induced hepatotoxicity. Protein iso-late of P. niruri was intraperitoneally injected in mice either prior to (preventive) or after the induction of toxicity (curative). Levels of different liver marker enzymes in serum were measured in normal, control (toxicity induced) and protein isolate treated mice. Protein isolate of P. niruri significantly reduced the elevated Glutamate Pyruvate Transaminase (GPT), and Lactate dehydrogenase (LDH) levels in sera of toxicity induced mice, compared to the control group. Treatment with the protein isolate of P. niruri also enhanced depleted hepatic glutathione (GSH) levels caused by APAP administration. In addition, histological studies supported these results and clearly showed that the protein isolate act as a hepatoprotective agent against APAP-induced toxicity. Combining, data suggest that the protein isolate of P. niruri protects liver tissues against APAP induced hepatic damage.