Objective To investigate the role of the microRNA miR-488-3p in homocysteine-mediated hepatocyte autophagy through targeted regulation of the RAS oncogene family member RAP1A. Methods Human normal hepatocytes(HL-7702) were routinely cultured in vitro and administered 100 μmol / L Hcy for 24 h. Western blot was used to detect expression levels of autophagy-related proteins LC3, p62 and RAP1A in hepatocytes, whereas qRT-PCR was used to detect the expression of miR-488-3p and RAP1A in these cells. Following transfection of miR-488-3p inhibitor and mimics, qRTPCR and western blot were used to detect the transfection efficiency of miR-488-3p and its effect on LC3 and p62 protein expression. TargetScan was used to predict the correlation between miR-488-3p and RAP1A genes, whereas western blotting was used to detect changes in the expression of RAP1A, a potential downstream target protein of miR-488-3p. Pearson’s correlation coefficient was used to evaluate potential correlations between expression levels of miR-488-3p and autophagy-related proteins in hepatocytes. Results Compared with the control group, expression levels of autophagyrelated proteins LC3, RAP1A and miR-488-3p in the Hcy group were increased (P<0. 01), whereas expression of p62 was significantly decreased (P<0. 01). Following administration of miR-488-3p inhibitor and mimics, expression levels of LC3 and RAP1A proteins in the miR-488-3p inhibitor group were significantly decreased (P<0. 01) and expression of p62 was significantly increased (P<0. 01) compared with the NC-inhibitor group. Compared with the NC-mimics group, expression levels of LC3 and RAP1A proteins in the miR-488-3p mimics group were significantly increased ( P < 0. 01 ), and expression of p62 was significantly decreased (P<0. 01). Further mechanistic studies showed that RAP1A is a downstream target gene of miR-488-3p that is positively regulated by this miRNA. Pearson’ s correlation analysis indicated that the expression level of miR-488-3p was positively correlated with protein expression of LC3 ( r= 0. 9329, P= 0. 0002), but negatively correlated with p62 protein expression ( r= - 0. 8086, P= 0. 0083). Conclusions miR-488-3p is highly expressed in Hcy-mediated hepatocytes and can promote their autophagy by targeting expression of RAP1A.