Objective To investigate whether the major histocompatibility complex class I chain-related gene A gene ( MICA) polymorphism and serum soluble MICA level were associated with the occurrence and development of colorectal cancer. Methods DNA samples from 117 colorectal cancer patients and 113 healthy individuals from Yangzhou in Jiangsu province were genotyped by using the polymerase chain reaction (PCR) and sequence-specific primer (SSP) method and PCR based sequencing. In addition, polymorphism at position 129 was also analyzed by PCR-SSP. Serum levels of soluble MICA were measured by a sandwich ELISA method. Results Neither the extracellular nor the transmembrane region polymorphisms of MICA gene were associated with the occurrence and the different stages of colorectal cancer. In contrast, the frequency of the methionine residue at position 129 was significantly decreased in the patient group. Soluble MICA levels in sera were increased in the late stages of colorectal cancer. Conclusion Although there was no genetic susceptibility attributed to MICA gene polymorphism with regard to development of colorectal cancer, serum levels of soluble MICA may be a diagnostic marker of advanced stages.