Here, we report that autophagy inhibition enhances the anti-tumor efficacy of a PI3K inhibitor in PIK3CA-mutant cervical cancer cells depending on the cellular context, in which forkhead box O3 (FOXO3a) nuclear translocation upon treatment with the PI3K inhibitor can induce cytoprotective autophagy, resulting in displaying the synergistic effect of autophagy inhibition with PI3K inhibitor. Here, PIK3CA is linked to cervical cancer.