Genomic studies of lung adenocarcinoma (LUAD) have advanced understanding of the disease’s biology and accelerated targeted therapy. However, proteomic characteristics of LUAD remain poorly understood. We carried out comprehensive proteomic analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer associated characteristics, such as tumor-associated protein variants, distinct proteomic features, and clinical outcomes in patients of early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90β as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomic analysis gives a more comprehensive understanding on the molecular landscape of LUAD and offers the opportunity for more precise diagnosis and treatment.