In this hospital-based case-control study, we found that the CT heterozygous, TT homozygous and combined (CT+TT) genotypes of GRP78 rs391957 polymorphism and the GA heterozygous, AA homozygous and combined (GA+AA) genotypes of GRP78 rs430397 polymorphism were both significantly associated with higher risk of CRC in a Chinese Han population, suggesting that the two GRP78 polymorphisms probably play potential roles in the development of CRC. Here, HSPA5 is linked to colorectal carcinoma.