In order to examine molecular markers of dysplasia progression, improved deoxycholate-trichloroaetic acid (DOC-TCA) extracted total protein of bronchial epithelial. After profiling squamous dysplasia versus invasive carcinoma of bronchial epithelium using two-dimensional electrophoresis, the patterns were compared and differential proteins were found with ImgeMaster software and Student t-test (P＜0.05). The selected differential protein-spots were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption /ionization time-of -flight mass spectrometry (MALDI-TOF-MS) and database searching. The average spots for dysplasia and invasive carcinoma were (1 273.00±43.31) and (1 326.00±66.63), respectively. After matching, the number of spots of differentially expressed proteins between the dysplasia and invasive cancer tissues were (56.00±8.96). Thirty eight differential proteins were identified, some of which are known to be involved in regulating the processes of proliferation, differentiation and tumorigenesis. In particular, c-Jun was up-regulated in invasive cancer compared with dysplasia, and murine double minute gene 2 (Mdm2) was only expressed in invasive cancer. But truncated EGFR (epidermal growth factor receptor) is reduced in invasive cancer. The subsequent immunohistochemical analysis of human tissues biopsies also showed a similar expression pattern. Therefore there are differentially expressed proteins during malignant transformation of bronchial epithelium from dysplasia to cancer. These differential proteins probably take part in carcinogenesis in different forms. The similar results of mass spectrometry and immunohistochemistry illustrated the use and reliability of comparative proteomics to screen relevant molecular markers of carcinogenesis.