Objective To investigate the relationship between 25-hydroxy vitamin D and colorectal neoplasms. Methods A case control study was designed to compare the plasma 25-hydroxy vitamin D levels of participants with colorectal cancer, progressive adenoma, adenoma, hyperplastic polyposis and healthy controls. Meanwhile, stratified analysis was carried out according to the lesion sites (proximal colon and distal colon). Results The plasma 25-hydroxy vitamin D was divided into three levels: ≤13.39, 13.39-18.23 and ≥18.23 ng/mL. The levels in colorectal cancer group (P<0.001), progressive adenoma group (P<0.001), adenoma group (P_trend<0.001), and hyperplastic polyposis group (P_trend=0.013) were all significantly lower compared to that in the healthy control group, with the OR (95%CI) values of highest value and the lowest value of vitamin D as follows: 0.33(0.21, 0.53), 0.18(0.09, 0.38), 0.09(0.01, 0.41), and 0.25(0.08, 0.77), respectively. After stratified according to the lesion sites, the plasma 25-hydroxy vitamin D levels of proximal colorectal cancer group (P_trend=0.001) and distal colorectal cancer group (P<0.001) were significantly lower than that of the healthy control group. The OR (95%CI) of highest value and the lowest value of vitamin D were 0.26(0.12, 0.56) and 0.33(0.20, 0.56), respectively. Conclusion Plasma 25-hydroxy vitamin D can reduce the risk of colorectal cancer regardless of the lesion locations.