ZnIn2S4　ultrathin　2D　nanosheets　with　a　positive　surface　charge　are　synthesized　by　a　hydrothermal　method　and　different　contents　of　surface　S　vacancies　are　induced　via　heat　treatment　of　as-prepared　ZnIn2S4　(ZIS).　As　the　S　vacancies　contents　increased,　the　photocatalytic　degradation　efficiency　of　ceftriaxone　(CTRX)　sodium　is　promoted.　Especially,　ZIS-300　shows　the　best　degradation　efficiency　(88.8%)　for　an　initial　CTRX　concentration　of　10　mg　L−1　in　2　h.　It　is　found　that　S　vacancies　cause　the　electron　density　of　surface　metal　atoms　(Zn,　In)　to　be　decreased,　which　makes　the　effective　adsorption　and　activation　of　ceftriaxone　anions　through　electrostatic　adsorption　interactions.　Meanwhile,　S　vacancies　also　serve　as　active　centers　to　promote　the　absorption　of　O2　and　gather　electrons　to　form　•O2−　species.　The　photogenerated　holes　quickly　transfer　to　the　surface　of　the　catalyst　to　directly　degrade　the　adsorbed　CTRX.　Thus,　the　photocatalytic　CTRX　degradation　efficiency　is　significantly　improved.　Finally,　a　possible　mechanism　for　over　defective　ZIS　is　proposed.　This　work　provides　a　feasible　strategy　for　the　efficient　degradation　of　antibiotics　from　the　perspective　of　electrostatic　adsorption　and　molecule　activation.　©　2022　Elsevier　Ltd