Objective: To investigate the relationship between interleukin 16 (IL-16) gene polymorphism and risk of colorectal cancer (CRC) in Han nationality population in China’s Shandong province. Methods: From 164 CRC patients and 121 control healthy subjects, two single nucleotide polymorphism (SNP) sites, rs11556218 and rs4778889, in the IL-16 gene sequence were genotyped by means of amplification refractory mutation system (ARMS)-PCR. The relations of the allele frequency and distribution of the two polymorphic sites with CRC risk were analyzed. Results: In group of CRC patients, both the T/G allele frequency and distribution of rs11556218 were significantly different from control group (P=0.021 725, P=0.001 033), but the differences in the T/C allele frequency and distribution of rs4778889 had no statistical significance versus control group (P=0.057 946, P=0.064 229). Conclusion: IL-16 rs11556218 gene polymorphism is probably associated with the increased CRC susceptibility.