Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a–4j were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, the most phototoxic compound 4d and 4j individually showed IC_(50) values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength(λ_(max)> 650 nm), high phototoxicity, low dark cytotoxicity and good water-solubility. Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a-4j were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compound examined higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD -MA. In particular, the most phototoxic compound 4d and 4j individually showed IC_ (50) values ​​of 41 nmol / L and 33 nmol / L against HCT116 cells, which showed 7.8- and 9.7-fold increase of antitumor potency compared to BPD- MA, respectively, suggesting that they were for photosensitizers for PDT applications due to their strong absorption at long wavelength (λ max (max)> 650 nm), high phototoxicity, low dark cytotoxicity and good water-solubility.