Objective: To explore the effects of long non-coding RNA CASC9 (LncRNA CASC9) on proliferation and apoptosis of A549 cells in non-small cell lung cancer (NSCLC) via AKT/mTOR pathway. Methods: Human NSCLC A549 cells were cultured in vitro and randomly divided into control group, LncRNA CASC9 overexpression group, LncRNA CASC9 siRNA group and LncRNA CASC9 si-NC group. After separate transfection of plasmid and siRNA, LncRNA CASC9 expression in each group was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) test was used to determine cell proliferation, flow cytometry (FCM) was used to detect cell apoptosis, and Western blot was used to detect the expression of apoptosis-related proteins of Bcl-2, Bax, caspase-3 and AKT/mTOR pathway protein in each group. Results: Compared with the control group, LncRNA CASC9 expression, apoptosis rate, Bax and caspase-3 protein expression decreased in LncRNA CASC9 siRNA group, while cell viability, Bcl-2 protein expression, p-AKT/AKT, p-mTOR/mTOR increased (p<0.05), LncRNA CASC9 expression, apoptosis rate, Bax and caspase-3 protein increased in LncRNA CASC9 overexpression group, while the cell vitality, Bcl-2 protein expression, p-AKT/AKT, p-mTOR/mTOR decreased (p<0.05). There was no significant difference in each index of A549 cells in LncRNA CASC9 siRNA negative control group (p>0.05). Conclusion: Up-regulation of LncRNA CASC9 can inhibit the proliferation and promote the apoptosis of A549 cells, which may be achieved by inhibiting the activation of AKT/mTOR pathway.