【Abstract】 Objective To explore the value of serum levels of miR-551b-3p and miR-143 in the diagnosis and prognosis of colonic adenocarcinoma. Methods In this clinical study, 87 patients with colonic adenocarcinoma (Observation group) and 106 patients with colonic polyps (Control group) were included. The fundamental and basic information were recorded. qPCR was used to analyze miR551b3p and miR-143 expressions in serum. Correlation between the serum level of miR551b3p and miR143, and clinic pathological features in the patients with colonic adenocarcinoma were analyzed. Results The serum level of miR-551b-3p and miR-143 were markedly lower in patients with colonic adenocarcinoma than in colonic polyps (P＜0.05 in all). The levels of miR551b3p and miR143 were negatively correlated with tumor differentiation, TNM stages, lymph node metastasis, and distant metastasis in patients with colonic adenocarcinoma (P＜0.05 in all). Conclusion In our study, the results indicated that miR-551b-3p and miR-143 probably involved in the proliferation, differentiation, and metastasis of colonic adenocarcinoma. Thus, miR551b3p and miR143 are the potential biomarkers in the diagnosis and prognosis of colonic adenocarcinoma. However, the large scale clinical investigation still needs to be implemented to confirm their value in the future.