Objective: To investigate the difference of microRNA expression profiles between colonic cancer without lymph node metastasis and the para-cancerous control, to identify the specific microRNA associated with the cancer and to predict the carcinogenetic mechanism of microRNA on the basis of these results. Methods: The microRNA (miRNA) were extracted and isolated from six specimens, including colonic cancerous and para-cancerous ones, all of which were confirmed to be without lymph node metastasis. Agilent microRNA microarrays consisting of 723 probes were used for screening the expression differences of microRNA. Data were analyzed using feature extraction software. The expression level of differentially expressed microRNA using quantitative real-time polymerase chain reaction (RT-PCR) was validated. RESULTS: A total of 14 miRNAs weRe found to be associated with colonic cancer, in which the expression of miR-106b, miR-135b, miR-18a, miR-18b, miR-196b, miR-19a, miR-224, miR-335, miR-424, miR-20a*, miR-301b and miR-374a were up-regulated and the expression of miR-378 and miR-378* were downregulated in colonic cancer tissues, compared with the para-cancerous control. The expression level of miR-18a and miR-135b were validated in accordance with the results of RT-PCR. Conclusion: The miRNAs are differentially expressed between colonic tumor tissues and para-cancerous tissues. Many of these miRNAs are expected to participate in the process of multiple tumorigenesis. These miRNAs could play an important role in the carcinogenesis of colon. These results provide new insights in human colorectal cancer genesis. © 2010 The Authors. Journal compilation © 2010 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology and Blackwell Publishing Asia Pty Ltd.