Due to the intensive commercial application of silver nanoparticles (Ag-NPs), their health risk assessment is of great importance. For acute toxicity evaluation of orally administered Ag-NPs, induction of reactive oxygen species (ROS), activity of liver function enzymes [(alanine (ALT/GPT), aspartate (AST/GOT), alkaline phosphatase (ALP)], concentration of lipid hydroperoxide (LHP), comet assay, and histopathology of liver in the rat model were performed. Four groups of five male rats were orally administered Ag-NPs, once a day for five days with doses of 5, 25, 50, 100 mg/kg, body weight. A control group was also made of five rats. Blood and liver were collected 24 h after the last treatment following standard protocols. Ag-NPs exposure increased the induction of ROS, activities of the liver enzymes (ALT, AST, ALP), concentration of lipid hydroperoxide (LHP), tail migration, and morphological alterations of the liver tissue in exposed groups compared to control. The highest two doses, 50 and 100 mg/kg showed statistically significant (p < 0.05) increases in ROS induction, ALT, AST, ALP activity, LHP concentration, DNA damage, and morphological alterations of liver compared to control. Based on these results, it is suggested that short-term administration of high doses of Ag-NP may cause organ toxicity and oxidative stress.