Objective：To investigate the role and mechanism of cardiolipin acyltransferase 1(ALCAT1)in Kirsten rat sarcoma viral oncogene homolog(KRAS)⁃ induced lung adenocarcinoma. Methods：In the animal experiments，the CC10rtta ⁃ KRAS mice were knocked out of the ALCAT1 gene，and induced lung adenocarcinoma with doxycycline diet. The occurrence of lung adenocarcinoma in mice was analyzed by micro⁃computed tomography(micro⁃CT)and HE staining. In the cell experiments，A549 cells were divided into the control group，Jenu group，hypoxia group and hypoxia + Jenu group，cobalt chloride(CoCl2)treatment was used to simulate hypoxic conditions，and ALCAT1 inhibitor Jenu was used to inhibit its enzymatic activity. The reactive oxygen species(ROS)and lactate levels were measured using kits in cells. Moreover，the mRNA transcription and protein expression of the related signal molecules were detected by RT ⁃ PCR and Western blot. Results：The results of animal experiments showed that ALCAT1 deficiency slowed the development of lung adenocarcinoma in mice and reduced lung tumor size. The results of cell experiments showed that Jenu significantly decreased the production of ROS and lactate under hypoxia，and down⁃regulated the expression of hypoxia inducible factor 1α(HIF1α)and the phosphorylation level of Akt. Conclusion：ALCAT1 deficiency could inhibit ROS generation and down⁃regulate HIF1α expression and Akt phosphorylation level，thereby improving the glycolysis metabolism in the tumor，ultimately preventing the development of lung adenocarcinoma.