Objective To investigate the relationship between IGF2BP3 hypomethylation with colon tumor differentia?tion. Methods Tissue samples from 41 colorectal cancer were collected from March 2011 to August 2011 in our hospital, among which 19 cases were well-differentiated adenocarcinoma, 12 cases were of moderately differentiated adenocarcinoma and 10 cases were of poorly differentiated adenocarcinoma. Meanwhile biopsy samples from 12 cases of colonic colitis were collected as a control. The expression of IGF2BP3 was assessed by immunohistochemistry and Western blot. An innovate of ELISA technique was used to examine global methylation levels while IGF2BP3 methylation level was tested by methylation specific PCR technique. Results The expressions of IGFBP3 are higher in all colon cancer groups than that in colitis (P<0.05). The expression of IGFBP3 in poorly differentiated adenocarcinoma is higher than that in all the other groups, but there is no significant difference between its expressions in the well differentiated group and in the moderately differentiated adeno?carcinoma group. The global DNA level and IGFBP3 methylation level of every colon cancer group is lower than those in coli?tis (P<0.05). Also, a tendency of decreasing global DNA and IGFBP3 methylation status was observed comparing well differ?entiated towards poorly differentiated carcinomas (P<0.05). Conclusion IGF2BP3 expression in colorectal cancer is asso?ciated with differentiation of colon cancer tissue. A lower global and IGF2BP3 DNA methylation suggest a worse differentia?tion of colon cancer. DNA hypomethylation may therefore play a regulatory role in the expression of IGF2BP3 in colon cancer tissue.