Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease’s biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics 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 proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and 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 proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment. Display omitted •Discovery of prognosis-associated proteins and pathways at early stage of LUAD•Proteomics revealed three subtypes related to clinical and molecular features•Identification of subtype-specific kinases and cancer-associated phosphoproteins•Identification of potential prognostic biomarkers and drug targets in LUAD Integrative proteomic characterization of lung adenocarcinoma in 103 Chinese patients identifies three subtypes related to clinical and molecular features and nominates potential prognostic biomarkers and drug targets.