Objective To observe the regulation of Panx1 on ATP/IP3 signaling pathway and its mechanism during cisplatin-induced apoptosis of lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line A549 was used as the research object and carbenoxolone (CBX) was used as a drug interference tool. A549 cells were divided into normal control group, the CBX group, the cisplatin (DDP) group and the CBX+DDP group. MTT assay and Annexin V/PI assay were used to detect the survival and apoptosis rates of A549 cells. The relative concentrations of extracellular adenosine triphosphate (ATP) and intracellular inositol triphosphate (IP3) were measured by Chemiluminescence and ELISA. Results Compared with DDP group, the cell survival rate of CBX+DDP group increased, while the early and late apoptotic rates and the release concentration of extracellular ATP and intracellular IP3 decreased (all P < 0.01). Conclusion Panx1 can increase the sensitivity of lung adenocarcinoma cells to cisplatin by regulating the ATP/IP3 signaling pathway.