Colorectal carcinoma (CRC) is one of the most common cancers in the world, and identification of new CRC biomarkers will be helpful for the diagnosis and treatment of CRC. For isobaric tags for relative and absolute quantitation (iTRAQ) analysis, fresh CRC and adjacent, colonic adenoma, ulcerative colitis, Crohn's disease and noncancerous colonic epithelial tissue were obtained from patients at the 2nd Xiangya Hospital of Central South University, China. The function of heterogeneous nuclear ribonucleoprotein M (HnRNP M) during the proliferation, invasion and metastasis of colorectal carcinoma cells in vitro were evaluated. One hundred and twenty-six differentially expressed proteins were identified by iTRAQ analysis. The expression of HnRNP M exhibited progressive changes during the carcinogenic process, and was validated by western blot. The up-regulation of HnRNP M correlated with cancer recurrence and regional lymph nodes. Furthermore, biological role exploring suggests that HnRNP M positively regulates cell cycle progression, promotes cell growth and invasion in vitro and increases the colony-forming ability of LS174T cells. The present data demonstrate that the up-regulation of HnRNP M is involved in human colorectal epithelial carcinogenesis and may serve as a carcinoma biomarker for CRC.