In this study, we mainly focus on probing expression profile and detailed functions of long non-coding RNA TFAP2A antisense RNA 1 (TFAP2A-AS1) in non-small cell lung cancer (NSCLC). Moreover, the mechanisms played by TFAP2A-AS1 were unraveled comprehensively. Herein, a notable overexpressed TFAP2A-AS1 in NSCLC was observed by TCGA and our own cohort. An increased TFAP2A-AS1 level displayed a negative correlation with the overall survival of patients with NSCLC. Loss-of-function approaches illustrated that the absence of TFAP2A-AS1 weakened NSCLC cell proliferation, colony formation, migration and invasionin vitro. Also, interference of TFAP2A-AS1 causedin vivotumor growth suppression. Mechanistically, TFAP2A-AS1 could negative regulate microRNA-584-3p (miR-584-3p) as a competitive endogenous RNA. Furthermore, cyclin-dependent kinase 4 (CDK4), a direct target of miR-584-3p, was positively controlled by TFAP2A-AS1 in a miR-5184-3p-dependent manner. Rescue function experiments corroborated that the anticancer activities of TFAP2A-AS1 deficient on the oncogenicity of NSCLC cells were reversed by downregulating miR-584-3p or overexpressing CDK4. To sum up, TFAP2A-AS1 exhibits cancer-promoting roles in NSCLC through the adjustment of miR-584-3p/CDK4 axis.