To study the expression of differential methylation-associated Staufen gene in colorectal cancer (CRC), we detected the expression of Staufen gene in adenocarcinoma, mucosa adjacent to colorectal cancer (MACC) and corresponding distant normal tissue using RT-PCR and immunohistochemistry. We found that the expression of Staufen gene in MACC and adenocarcinoma of CRC was significantly lower than that in corresponding distal normal tissue at mRNA level (P<0.05.No significant associations were found between age, sex, location of cancer (colon/rectal), degree of differentiation and metastasis of lymph node with expression of Staufen gene. Lower expression of Staufen protein in MACC was verified by comparing with matched normal tissue and adenocarcinoma (P<0.05). This study indicated low expression of Staufen gene in colorectal cancer and the Staufen gene might be involved in the development of colorectal cancer.