Objective:To discover the characteristics of the gene expression profile of primary ACC and MEC in the lungs by sequencing and comparing DNA and RNA of primary adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) of the lung. Methods: 14 cases of lung ACC and 24 cases of lung MEC were enrolled. After extracting DNA and RNA, DNA and RNA transcription group were used to gene sequencing and bioinformatics analysis. Results: Among the detected DNA mutations in cancer tissues, MYB/MYBL1 fusion was detected in 78.5% lung ACC patients. The most common mutation in lung MEC patients was MAML2 rearrangement, and 3 MEC patients had EWSR1 fusion, and 1 case ROS1 fusion occurs in MEC patients. Among the RNA differential genes in cancer tissues and adjacent tissues, SOX10 and BCL11A are highly expressed in lung ACC, and the most differentially expressed gene in lung MEC is TFAP2A. Conclusions: In addition to the most common MAML2 mutations in lung MEC gene mutations, EWSR1 fusion and ROS1 mutations have also been newly discovered. The most common lung ACC gene mutations are MYB/ MYBL1 fusion,which were reported in salivary gland ACC. Combined with previous studies on salivary gland ACC and lung cancer, SOX10 and BCL11A may become new biomarkers of lung ACC. TFAP2A is related to lung MEC resistance to anlotinib.