miR-122 and miR-192 were investigated as indicators of toxic liver injury caused by acetaminophen, but their role in idiosyncratic toxic liver injury remains controversial.So, this work aimed to assess and compare the expressions of miR-122 and miR-192 in two different types of toxic liver injury (intrinsic [acetaminophen] and idiosyncratic [diclofenac]). Forty male adult Wistar albino rats were divided into equal five groups, in which serum liver enzymes; microRNAs (miRNAs) expressions (miR-122 and miR-192) and histopathological findings were studied. The present study showed that (1) miR-122 and miR-192 are good serum biomarkers of toxic liver injury whatever its etiology, as their serum levels exhibited a significantly earlier increase and earlier return to normal baseline levels as compared to serum aminotransferase levels;(2) miR-122 is more specific than miR-192; and (3) both serum levels of miR-122 and miR-192 showed non-significant differences in relation to the type of toxic liver injury. K E Y W O R D S biomarkers, hepatotoxicity, idiosyncratic, intrinsic, miR-122, miR-192, real-time polymerase chain reaction J Biochem Mol Toxicol. 2019;33:e22321. wileyonlinelibrary.com/journal/jbt