Selenium nanoparticles (SeNPs) have been widely used as anti-inflammatory and anti-toxic agent. The present study used Bacillus tequilensis for biosynthesizing SeNPs from sodium selenite (Na 2 SeO 3 ) and investigated its ameliorative effects on acetaminophen (APAP) hepatotoxicity in male mice. The results indicated that Alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) significantly elevated in mice treated with APAP, while other liver markers (total proteins and albumin) did not change. SeNPs either alone or in combination with APAP showed ameliorative effects on liver enzymes to some extents where their activities decreased to be insignificant with those of normal group. A slight variation was shown in total antioxidant capacity (TAC). Histopathologically, the hepatocytes of the mice treated with APAP showed cloudy swelling and vacuolar degeneration, while those treated with SeNPs or both SeNPs and APAP appeared more or less histologically normal. In conclusion, SeNPs can be used to improve or replace today's therapies of APAP hepatotoxicity.