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AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.METHODS: Colon tissues (normal and cancerous)were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.