Abstract: Tetrahydrocurcumin (THC), a hydrogenated derivative of curcumin (CUR), exhibits superior molecular stability and pharmacokinetic properties owing to its optimized molecular structure, as well as enhanced accumulation in tumor tissues compared with CUR. Moreover, THC can enhance therapeutic efficacy and reduce toxicity when combined with conventional radiotherapy, chemotherapy, or immunotherapy. Advances in drug delivery systems, including solid dispersions and targeted nanocarriers, have further improved its tumor-targeting efficiency. However, research on the application of THC in cancer therapy remains limited, and its clinical translation faces considerable challenges. This review systematically summarizes recent advances in the application of THC in cancer therapy, with a focus on its multitarget mechanisms of action, including the induction of tumor cell apoptosis, inhibition of tumor invasion and metastasis, and modulation of the tumor immune microenvironment through the regulation of signaling pathways involved in cell proliferation, metabolism, and autophagy. It also highlights the key advantages and translational potential of THC as a promising antitumor agent, with the aim of providing new insights into precision cancer therapy.