Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancer occurrences and is divided into largely Adenocarcinoma (LUAD), Squamous cell carcinoma (LUSC), and Large cell carcinoma. In this study, using RNA-seq data between cancer tissues and adjacent normal tissues of 5 LUAD and 4 LUSC patients, we found that a Death associated protein like 1 (DAPL1) was highly expressed in squamous cell carcinoma but not in adenocarcinoma. Through the RNA-seq analysis, we found that lipid metabolic pathway genes Fdft1, Pcyt1a, and Sptlc1 correlate well with DAPL1 level changes in LUSC. We also found that Dapl1 was activated by Np63 and GRα monomer transcription factors. We generated a DAPL1 knockout mouse, which shows body weight and hair color changes, implying the role of DAPL1 in lipid metabolism. Our data show that Np63, GRα transcription factors activate DAPL1, and it is predicted to contribute to cellular acidification by regulating lipid metabolism based on mRNA-seq data and DAPL1 KO mice.