Four novel porphyrins containing nitric oxide (NO) donors were synthesized, and the structures of all the products were characterized by IR, UV-vis, (1)H NMR, and elementary analysis. Interestingly, these new compounds not only were able to release NO, but also showed cancer cell-oriented accumulation. Higher accumulation of these new porphyrins containing NO donors in BEL-7402 liver cancer cells than in L-02 liver normal cells was corroborated by UV-vis spectroscopy. The biological activity of these porphyrins against BEL-7402 liver cancer cells was tested with a MTT assay. The studies indicated that they had more effective killing of BEL-7402 liver cancer cells than that of L-02 liver normal cells, and they had similar activity against MCF-7 breast cancer cells when compared to 5-fluorouracil in the absence of light.