Pathological features of hepatoid adenocarcinoma of the lung (HAL) are similar to those of hepatocellular carcinoma (HCC) and HAL has a poor prognosis. In this study, we aimed to elucidate clinicopathologic and molecular features of HAL.Four cases of HAL patients with one lobe of the lung resected were enrolled into the study. Next generation sequencing (NGS) of a 425-gene panel was performed on tumor tissue samples.The most frequently mutated gene was TP53 in three cases of primary HAL and one case of metastatic HAL, with a mutation rate of 100%. Also, CDK8, CDKN2A, EPHA5, SMARCA4, and STK11 were detected as high-frequency mutations, with a mutation rate of 50%. The types of TP53 mutation included two missense variants and two frameshift ones. The TP53 mutation was related to the occurrence of HAL.HAL could be caused by genetic mutations and is closely related to TP53 mutation.