Purpose:Although growing studies have reported the disturbances of trace elements (TEs) homeostasis was closely associated with the occurrence of colorectal cancer (CRC), the clinical value of TEs in CRC with different molecular subtypes was largely unknown. This study aimed to explore the correlation betweenKRASmutations/MSI status and serum TEs levels in patients with CRC.Methods:The serum concentrations of 18 TEs were detected by inductively coupled plasma emission spectrometry (ICP-MS). MSI status (two mononucleotides: BAT25, BAT26, three dinucleotides: D2S123, D5S346, and D17S250),KRAS(G516T, G517A, G518C, G520T, G521A, G522C, and G532A) mutations were detected by the multiplex fluorescent PCR and the real-time fluorescent quantitative PCR, respectively. The correlations amongKRASmutations/MSI status, demographic and clinical characteristics, and TEs were analyzed by Spearman correlation analysis.Results:The propensity score matching (PSM) analysis was adopted to minimize differences between groups. Before PSM, 204 CRC patients were recruited in this study, including 123KRAS-negative patients and 81KRAS-positive patients according to the test results ofKRASmutations, and 165 MSS patients and 39 MSI patients based on MSI detection. After PSM, the serum concentration of Mn was significantly lower in CRC patients withKRASmutations than those withoutKRASmutations, and a significant negative correlation was observed between Mn and Pb in theKRAS-positive cases. CRC patients carrying MSI had a significantly lower level of Rb compared to MSS patients. Importantly, Rb was significantly positively correlated with Fe, Mn, Se, and Zn in patients with MSI. Collectively, all our data indicated that the occurrence of different molecular events might be accompanied by different alterations in types and levels of serum TEs.Conclusions:CRC patients with different molecular subtypes presented different alterations in types and levels of serum TEs. Mn was significantly negatively correlated with theKRASmutations, and Rb was noticeably negatively correlated with the MSI status, indicating certain TEs might contribute to the pathogenesis of molecular subtype-specific colorectal cancer.