Objective: To investigate the significance of epithelial-mesenchymal transition (EMT) of human colorectal cancer cells with resistance to chemoradiotherapy. Methods: Colorectal cancer cells were exposed to 5-fluorouracil (5-FU) while radiotherapy was given at the same time. A small number of cells that survived from chemoradiotherapy were obtained, and their morphological changes were observed by microscopy. Our group then identified the resistance using colony formation assay. Real-time PCR and Western blot were used to detect the mRNA and its protein expression of epithelial marker E-cadherin, mesenchymal marker N-cadherin, vimentin, and nuclear transcription factor snail. Results: Colorectal cancer cells which were resistant to chemoradiotherapy showed phenotypic changes consistent with EMT: spindle-cell shape, loss of polarity, and pseudopodia formation. Real-time PCR and Western blot results: E-cadherin mRNA and protein expression level were lower, and N-cadherin, Snail, vimentin mRNAs and proteins expression level were higher, the difference was statistically significant (P<0.05). Conclusion: Colorectal cancer cells resistance to chemoradiotherapy can induce epithelial-mesenchymal transition (EMT), and EMT may be related to resistance of chemoradiotherapy of colorectal cancer.