Abstract： Objective To analyze differential expression proteins of human colon cancer Lovo cell line treated by oxaliplatin, and to explore the antitumor mechanism of oxaliplatin in the view of proteomics perspective. Methods The Lovo cells were randomly divided into two groups, including the experimental group (cultured in oxaliplatin- containing solution) and the control group (cultured in oxaliplatin-free solution). After culture, the both groups were processed by two-dimensional gel electrophoresis to select disparates, and differential proteins were identified by mass spectrometry analyses. Results High resolution and good reproducibility were observed on electrophoretograms of both groups, with matching rates at 80.16% (812/1013) and 81.19% (829/1021) respectively. Twenty-two repeated disparate points were obtained, ten of them were selected for mass spectrometry analyses. Six colorectal cancer related proteins were successfully identified, including 3 up-regulated proteins (β-2 microglobulin, splicing factor SFRS3 and uracil-DNA glycosylase) and 3 down-regulated proteins (60 S acidic ribosomal protein, glyceraldehyde-3-phosphate dehydrogenase and guanine nucleotide binding protein β polypeptide 2-like 1). Conclusion Multiple differential protein expressions are identified in human colon cancer Lovo cell line after oxaliplatin treatment, and the proteins are related to immune enhancement, pre-mRNA transcription modification, DNA damage repair, protein translation regulation, post- translation processing, metabolism of energy and signaling transduction pathway.