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Expression of miR-34c and miR-141 in serum of colon cancer patients and their association with clinicopathological features and diagnostic value for colon cancer were investigated. A total of 64 patients with colon cancer admitted to Hubei Cancer Hospital from January 2016 to March 2018 were included in the experimental group, and 64 healthy subjects undergoing physical examination during the same period were the control group. The expression of miR-34c and miR-141 in serum of patients in the two groups were detected by RT-qPCR, and the association of miR-34c and miR-141 with the clinicopathological characteristics of colon cancer patients was analyzed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of miR-34c and miR-141 in colon cancer. The expression of miR-141 in serum of patients in the experimental group was significantly higher than that in the control group (P<0.05). Expression of miR-34c in serum of patients in the experimental group was significantly lower than that in the control group (P<0.05) and the expression of miR-34c and miR-141 in serum of the experimental group were associated with tumor diameter, clinical stage, degree of differentiation and lymph node metastasis (P<0.05). AUC of serum miR-34c in the diagnosis of colon cancer was 0.857 (95% CI: 0.795-0.919), with the cut-off value of 0.800, the diagnostic sensitivity of 84.38%, and the specificity of 68.75% and AUC of serum miR-141 in the diagnosis of colon cancer was 0.876 (95% CI: 0.810-0.941), with the cut-off value of 0.282, the diagnostic sensitivity of 70.31%, and the specificity of 96.88%. The ROC curve for the diagnosis of colon cancer was further plotted in combination with serum miR-34c and miR-141. AUC of the two combined for the diagnosis of colon cancer was 0.929 (95% CI: 0.884-0.974), with the cut-off value of 0.566, the diagnostic sensitivity of 84.38%, and the specificity of 93.75%. In conclusion, miR-34c and miR-141 might be involved in the occurrence and progression of colon cancer and could be used as biological indicators for early diagnosis of colon cancer. [ABSTRACT FROM AUTHOR]