We proposed a systems biology framework integrating mathematical model and network biology to elucidate how forkhead box class O (FOXOs) FOXO1 and FOXO3a serve as critical regulators linking cGAS–STING signaling with interleukin-6 (IL-6) in promoting autophagy in NSCLC. Here, STING1 is linked to non-small cell lung carcinoma.