Abstract: Objective To investigate the effect of miR-27a on Streptococcus pneumoniae ( SP) -induced injury of HPAEpiCs by regulating autophagy mediated by the PI3K/ AKT / mTOR pathway. Methods HPAEpiCs were infected with 1× 108 CFU/ mL SP. At 48 hours before induction the cells were transfected with miR-27a-NC ( miR-27a-NC group) , miR-27a-inhibitor ( miR-27a-inhibitor group) , pcDNA-NC ( pcDNA-NC group) or pcDNA-PI3K ( pcDNA- PI3K group) or cotransfected with miR-27a-NC and Si-NC (miR-27a-NC+Si-NC group) , miR-27a inhibitor and Si-NC (miR-27a inhibitor+Si-NC group) , miR-27a-NC and Si-PI3K (miR-27a-NC+Si-PI3K group) , or miR-27a-inhibitor and Si-PI3K (miR-27a-inhibitor+Si-PI3K group) using a Lipofectamine 3000 transfection kit. Non-induced cells were used as the control group, and induced, but untransfected, cells were used as the induction group. qRT-PCR was used to measure the expression level of miR-27a in normal and SP-induced alveolar epithelial cells. Bioinformatics prediction and dual luciferase assays were used to verify the targeting relationship between miR-27a and PI3K. CCK-8 Assays was used to assess proliferation activity. Flow cytometry was used to measure the apoptosis rate. ELISA were used to detect the contents of IL-6 and IL-10 in culture supernatants. Western blot was used to measure the expression levels of PI3K and Beclin1, the LC3-II/ I ratio and the phosphorylation levels of AKT and mTOR. Results Compared with the control group, the expression level of miR-27a, apoptosis rate, IL-6 content, Beclin1 protein expression level and LC3-II/ I ratio were higher in the induction group (P<0. 05) and the PI3K protein expression level, cell proliferation rate, IL-10 content and phosphorylation levels of AKT and mTOR were lower (P<0. 05) . Compared with the miR-27a-NC group, the expression level of miR-27a, apoptosis rate, IL-6, Beclin1 protein expression level and LC3-II/ I ratio were lower in the miR-27a-inhibitor group content ( P< 0. 05) , the cell proliferation rate, content of IL-10, the protein phosphorylation levels of AKT and mTOR were higher ( P< 0. 05) . Compared with the pcDNA-NC group, the apoptosis rate, IL-6 content, Beclin1 protein expression level and LC3-II/ I ratio were lower in the pcDNA-PI3K group ( P< 0. 05) and the PI3K protein expression level, cell proliferation rate, IL-10 content and phosphorylation levels of AKT and mTOR were higher (P<0. 05) . Conclusions During injury of HPAEpiCs induced by SP, miR-27a inhibits the PI3K/ AKT / mTOR signaling pathway and promotes autophagy. Inhibition of miR-27a activates the PI3K/ AKT / mTOR signaling pathway, inhibits autophagy and alleviates SP-induced injury of HPAEpiCs.