The aim of this study was to investigate whether inhibiting liver-PTP1B and LMPTP in human hepatocytes with MSI-1436 and compound 23 (N,N-diethyl-4-(4-((3-(piperidin-1-yl)propyl)amino)quinolin-2-yl) benzamide), over the course of an experimental lipotoxic status induced by a combination of two free fatty acids (namely, palmitate and oleate) can protect cells from lipoapoptosis, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress, which are salient features of NAFLD. This evidence concerns the gene PTPN1 and metabolic dysfunction-associated steatotic liver disease.