The androgen receptor (AR) plays a crucial role in the physiological and pathological functions of androgen. As a transcription factor, the AR modulates androgen activity by regulating the transcription of target genes that are involved in numerous physiological functions and pathological disorders, such as acne vulgaris, androgenetic alopecia, benign prostate hyperplasia (BPH), and prostate cancers. Although many natural and synthetic curcumin analogues have been reported to possess anticancer activity through a common cytotoxic property against proliferating tumor cells, none has been reported to inhibit cancer cell growth through a more specific mechanism or target in the cancer cells. Recently, new curcumin analogues were studied extensively regarding their synthesis, structure-activity (i.e., anticancer activity) relationships, and mechanism of action. These compounds, such as ASC-J9 and its analogues (3 and 4), have now been shown to inhibit prostate cancer proliferation through a novel mechanism of enhancing AR degradation.