Colorectal cancer is one of the most common cancers worldwide. The role of tight junction proteins in the development of this disease is currently well known. Among the large claudin family, seven representatives are involved in tumorigenesis. This review aims to analyze published data on the molecular genetic mechanisms of CLDN7 involvement in colorectal cancer pathogenesis. We summarize current information on the molecular mechanisms regulating CLDN7 expression in normal conditions and in colorectal cancer. We found that CLDN7 expression can be regulated by several mechanisms, including transcription, epigenetic and post-translational modifications modulated by oncogenic signaling pathways. Increased CLDN7 expression induces mesenchymal-to-epithelial transformation, thereby inhibiting tumorigenesis by influencing the Wnt/β-catenin, Notch, Hippo, p53, and other signaling pathways. Low expression or loss of CLDN7 expression is associated with late-stage disease and higher tumor grade. However, epigenetic regulation through methylation and microRNAs, leading to decreased CLDN7 levels, along with post-translational modification by palmitoylation and phosphorylation, promotes colorectal cancer progression. Incorporating data from molecular genetic studies on the mechanisms regulating tight junction protein function is essential for developing modern treatments for patients with colorectal cancer.