ObjectiveTo investigate the relationship among 18 heavy metals, microsatellite instability (MSI) status,ERCC1,XRCC1 (rs25487),BRAF V600Eand 5 tumor markers and their role in the development of colorectal cancer (CRC).MethodsA total of 101 CRC patients and 60 healthy controls were recruited in the present study. The levels of 18 heavy metals were measured by ICP-MS. MSI status and the genetic polymorphism were determined by PCR (FP205-02, Tiangen Biochemical Technology Co., Ltd., Beijing, China) and Sanger sequencing. Spearman’s rank correlation was used to analyze the relationship among various factors.ResultsThe level of selenium (Se) was lower in the CRC group compared with the control group (p < 0.01), while vanadium (V), arsenic (As), tin (Sn), barium (Ba) and lead (Pb) were higher (p < 0.05), chromium (Cr) and copper (Cu) were significantly higher (p < 0.0001) in the CRC group than those in the control group. Multivariate logistic regression analysis indicated that Cr, Cu, As and Ba were the risk factors for CRC. In addition, CRC was positively correlated with V, Cr, Cu, As, Sn, Ba and Pb, but negatively correlated with Se. MSI was positively correlated withBRAF V600E, but negatively correlated withERCC1.BRAF V600Ewas positively correlated with antimony (Sb), thallium (Tl), CA19-9, NSE, AFP and CK19.XRCC1 (rs25487)was found to be positively correlated with Se but negatively correlated with Co. The levels of Sb and Tl were significantly higher in theBRAF V600Epositive group compared to the negative group. The mRNA expression level ofERCC1was significantly higher (P = 0.035) in MSS compared to MSI. And there was a significant correlation betweenXRCC1 (rs25487)polymorphism and MSI status (P<0.05).ConclusionThe results showed that low level of Se and high levels of V, As, Sn, Ba, Pb, Cr, and Cu increased the risk of CRC. Sb and Tl may causeBRAF V600Emutations, leading to MSI.XRCC1 (rs25487)was positively correlated with Se but negatively correlated with Co. The expression ofERCC1may be related to MSS, while theXRCC1 (rs25487)polymorphism is related to MSI.