DGCR5 was upregulated in LUAD tissues and LUAD cell lines.Inhibition of DGCR5 can prevent LUAD progression via playing anti-apoptosis roles.Both mRNA expression and protein levels of BCL-2 were increased by DGCR5 downregulation while reversely BAX was increased. Additionally,a novel microRNA target of DGCR5,hsa-mir-22-3p was identified through bioinformatics search and confirmed by dual-luciferase reporter system. Gain and loss-of-function studies were performed to verify whether DGCR5 exerts its biological functions through regulating hsa-mir-22-3p in vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of hsa-mir-22-3p mimics. Furthermore, in vivo tests tumor xenografts were established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated DGCR5 expression was greatly associated with smaller tumor size,implying a favorable prognosis of LUAD patients.Taken these together,DGCR5 could be considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and treatment.