Cystatin SN (cystatin 1, CST1) is a member of the cystatin superfamily which inhibits the proteolytic activity of cysteine proteases. CST1 is a tumor biomarker that provides useful information for the diagnosis of esophageal, gastric and colorectal carcinomas. MicroRNAs (miRNAs or miRs) play an important role in tumor cell proliferation. However, the exact role of let‑7d and CST1 in colon cancer remains unknown. The aim of this study was to assess whether let‑7d inhibits colorectal carcinogenesis through the CST1/p65 pathway, and determine whether it may be used as a potential target for clinical therapy. Microarray analysis of mRNAs extracted from colon cancer and normal tissues was performed. The results of gene expression microanalysis revealed that CST1 expression was upregulated in colon cancer compared with normal tissues. In addition, the upregulation of CST1 expression and the downregulation of let‑7d expression in patients with colon cancer and in several colorectal cancer cell lines were confirmed by reverse transcription-quantitative PCR (RT‑qPCR), immunohistochemistry and western blot analysis. In addition, siRNA targeting CST1 (CST1‑siRNA) and let‑7d-mimics were used in the HCT116 cells, and the results revealed that CST1 and let‑7d played a role in colorectal cancer cell proliferation. Let‑7d inhibited colorectal carcinogenesis through the CST1/p65 pathway. Thus, the findings of the present study indicate that CST1 may be a potential target for the future clinical therapy of colorectal cancer.