The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 μg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals. Alleviated activities of adenosine triphosphatase (ATPase), glucose-6- phosphatase (G6Pase) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase (CAT) due to APAP induced toxicity in liver were recovered by the treatment of AgNPs. Improvement in histoarchitecture of liver was also consistent with biochemical observations. The results revealed that AgNPs showed significant dose-dependent protection against APAP induced hepatocellular injury.