Antimicrobial　peptides　(AMPs)　are　originally　developed　for　anti-infective　treatments.　Because　of　their　membrane-lytic　property,　AMPs　have　been　considered　as　candidates　of　antitumor　agents　for　a　long　time.　However,　their　antitumor　applications　are　mainly　hampered　by　fast　renal　clearance　and　high　systemic　toxicities.　This　study　proposes　a　strategy　aiming　at　addressing　these　two　issues　by　conjugating　AMPs　with　porphyrins,　which　bind　to　albumin　increasing　AMPs＇　resistance　against　renal　clearance　and　thus　enhancing　their　antitumor　efficacies.　Porphyrins＇　photodynamic　properties　can　further　augment　AMPs＇　antitumor　effects.　In　addition,　circulating　with　albumin　ameliorates　AMPs＇　systemic　toxicities,　i.e.　hemolysis　and　organ　dysfunctions.　As　an　example,　we　conjugated　an　AMP,　K6L9,　with　pyropheophorbide-a　(PPA)　leading　to　a　conjugate　of　PPA-K6L9.　PPA-K6L9　bound　to　albumin　with　a　K-D　value　at　the　submicromolar　range.　Combining　computational　and　experimental　approaches,　we　characterized　the　molecular　interaction　of　PPA-K6L9　with　albumin.　Furthermore,　PPA-conjugation　promoted　K6L9＇　antitumor　effects　by　prolonging　its　in　vivo　retention　time,　and　reduced　the　hemolysis　and　hepatic　injuries,　which　confirmed　our　design　strategy.　(C)　2021　Elsevier　Masson　SAS.　All　rights　reserved.