By integrating the lipidome and transcriptome results, genes related to differential lipid metabolites in Kazakh ESCC patients were identified, and the effects of the key gene AMPK on lipid metabolism in ESCC cells were investigated by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC‒MS/MS). Here, PRKAA2 is linked to esophageal squamous cell carcinoma.