An effective therapeutic target is imperative for cancer treatment, including gene therapy. 14-3-3zeta, a member of the 14-3-3 protein family, acts as a suppressor of apoptosis and has a central role in tumor genesis and progression. Owing to its wide upregulation in human tumors and its involvement in cancer progression and treatment resistance, 14-3-3zeta is currently undergoing extensive investigation as a novel therapeutic target. In this review, we widely investigate the role of 14-3-3zeta in cancer and suggest a potential therapeutic target for new anticancer interventions.