Cellular homeostasis in many organs is maintained via gap junctions composed of connexin (Cx), a large protein family with a number of isoforms. In fact, gap junctional intercellular communication (GJIC) is actively involved in all aspects of the cellular life cycle, ranging from cell growth to cell death. It has been well known that Cx gene acts as a tumor suppressor gene due to the maintenance of cellular homeostasis via GJIC. On the other hand, recent data show that GJIC-independent function for Cx gene contributes to tumor-suppressive effect of the gene with cell certain specificity. However, the mechanistic aspect of the GJIC-independent function remains largely unknown. In this review, we briefly summarize the tumor-suppressive effects of Cx genes, refer to a new aspect of Cx32 as an anti-invasive and anti-metastatic gene against renal cell carcinoma in a GJIC-independent function and establishment of a new cancer therapy based on the new function of Cx32.