Abstract Background. Colorectal cancer guidelines recommend adjuvant chemotherapy is based on the number of lymph nodes metastasis. Let-7a-5p is a microRNA which could inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2. The aim of this study was to investigate the role of let-7a-5p in clinical impact of colorectal cancer (CRC). Methods. One hundred ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serums and tumor tissues were analyzed by real-time PCR and immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence. Results. The expression of let-7a-5p in tumor tissues was significantly negative correlated with tumor size, stage, and lymph node metastasis in CRC patients (p = 0.024 for tumor size, p = <0.0001 for stage, and p<0.0001 for lymph node metastasis). There was a negative correlation between levels of let-7a-5p and the HMGA2 gene (p <0.0001), especially in CRC patients with wildtype APC gene. Patients with let-7a-5p low / HMGA2 high had poorer overall survival (OS) and disease-free survival (DFS) rates than those with let-7a-5p high / HMGA2 high, let-7a-5p high / HMGA2 low, and let-7a-5p low /HMGA2 low groups. In addition, the expression levels of let-7a-5p in PBMCs were positive correlated with in tumor tissues of CRC patients. Conclusion. We suggest that down-regulation of let-7a-5p in PBMCs and tumor tissues patients could be used to predicts lymph node metastasis and prognosis impact on chemotherapy of colorectal cancer Citation Format: Ya-Wen Cheng, Tsang-Pai Liu, Po-Li Wei, Huei Lee. Downregulation of let 7a 5p predicts lymph node metastasis and prognosis in colorectal cancer: implications for chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3410.