In this study, we investigated the effects of aaptamine on non-small cell lung carcinoma (NSCLC) cells growth and progression and dissected the mechanism underlying the anticancer functions via specific degradation of the phosphorylated AKT and GSK3β in PI3K/AKT/GSK3β signal axis, which subsequently abated the cell cycle regulation drivers (CDK2/4 and Cyclin D1/E). Here, CCND1 is linked to non-small cell lung carcinoma.