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Since tyrosine kinase inhibitor (TKI) could reverse ABCG2-mediated drug-resistance, novel chlorin e 6 -based conjugates of Dasatinib and Imatinib as photosensitizer (PS) were designed and synthesized. The results demonstrated that conjugate 10b showed strongest phototoxicity against HepG2 and B16-F10 cells, which was more phototoxic than chlorin e 6 and Talaporfin. It could reduce efflux of intracellular PS by inhibiting ABCG2 in HepG2 cells, and localize in mitochondria, lysosomes, golgi and ER, resulting in higher cell apoptosis rate and ROS production than Talaporfin. Moreover, it could induce cell autophagy and block cell cycle in S phase, and significantly inhibit tumor growth and prolong survival time on BALB/c nude mice bearing HepG2 xenograft tumor to a greater extent than chlorin e 6. Consequently, compound 10b could be applied as a promising candidate PS due to its good water-solubility and stability, low drug-resistance, high quantum yield of 1O 2 and excellent antitumor efficacy in vitro and in vivo. [Display omitted] • The conjugates of chlorin e 6 with Dasatinib or Imatinib were synthesized. • In vitro PDT antitumor activities of all target compounds were investigated. • In vivo antitumor potency and mechanism of preferred compound 10b were evaluated. • In vitro PDT antitumor efficacy of 10b was better than chlorin e 6 and talaporfin. • In vivo PDT antitumor efficacy of 10b was superior to chlorin e 6. [ABSTRACT FROM AUTHOR]