Objective: To explore the effect of micro ribonucleic acid (miR)-506-3p on autophagy of renal tubular epithelial cells in sepsis and its mechanism.Methods: It was found through bioinformatics analysis that phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) was expressed at a low level in sepsis, and miR-506-3p had a targeted regulatory effect on PIK3CA. 40 8-week-old male C57BL/6 mice were randomly divided into control miR-506-3p NC group, control miR-506-3p OE group, sepsis miR-506-3p NC group, sepsis miR-506-3p OE group and sepsis miR-506-3p KD group. The pathological changes in kidney tissues of mice in each group were observed by hematoxylin-eosin (HE) staining and TUNEL staining, and mitochondria and autophagosomes were visualized by transmission electron microscopy. CCK8 assay was performed to detect the effect of miR-506-3p on the proliferation capacity of renal tubular epithelial cells. The changes in the expression of PI3K-Akt pathway proteins, mTOR and autophagy proteins were tested by Western blotting.Results: The injury and apoptotic positive cells were suppressed and decreased in miR-506-3p OE mice vs. NC group. miR-506-3p could increase the number of mitochondria and autophagosomes in kidney tissues. After introduction of exogenous miR-506-3p OE into renal tubular epithelial cells, the expressions of PI3K pathway proteins were significantly inhibited, while the expressions of autophagy proteins were significantly enhanced. After 740Y-P was added, the expressions of associated proteins had no significant changes in each group.Conclusion: Overexpression of miR-506-3p can enhance the autophagy of renal tubular epithelial cells in sepsis through inhibiting the PI3K signaling pathway.