Lung cancer is the leading cause of cancer deaths worldwide and is often diagnosed in the advanced or late stages. The discovery of candidate biomarkers in human lung cancer materials holds clinical potential as well as a significant challenge. Due to a large number of proteins in human materials that form the protein complexity and post-translational modifications (PTMs) of proteins, proteomic analysis of lung cancer biomarkers remains a difficult task. Many proteomic approaches have been used to investigate the biomarkers in human lung cancer materials. In this review, we summarize the current proteomic approaches employed for analysis of proteome profiles in human lung cancer materials and some PTMs causing different proteome profiles and expression levels of biomarkers in lung cancer. In addition, bioinformatic tools for PTMs are useful for prediction of glycosylation and phosphorylation sites in proteins, which can help us further understand the correlation of PTMs and tumor development. However, it is necessary that proteome analysis of lung cancer materials be incorporated with new strategies and technologies to improve the efficiency of the analysis and to investigate novel biomarkers that would be very useful for further diagnostic and therapeutic applications.