Riboflavin is a potent photosensitizer as well as part of the vitamin B complex. Recently we demonstrated that the products generated by irradiation of riboflavin have potential as anti-leukaemic therapy. The possible action, however, of the riboflavin photoproducts in solid cancers has not been addressed. Hence, we investigated the effects of irradiated riboflavin on androgen-independent human prostate cancer cells (PC3), a known model for solid tumour cells with an exceptional resistance to therapy. Our results show that riboflavin photoproducts are cytotoxic to these cells in a FasL-Fas-dependent manner. Furthermore, irradiated riboflavin inhibited matrix-degrading proteases, caused downregulation of VEGF and upregulation of TIMP1 suggesting anti-metastatic potential. Together, these results show that the anti-neoplastic action of riboflavin photoproducts is not limited to haematological malignancies, warranting clinical studies in solid tumours.