Attractive　results　have　been　achieved　with　small-molecule　target-based　drugs　in　the　anticancer　field;　however,　enhancing　their　treatment　effect　and　solving　the　problem　of　drug　resistance　remain　key　concerns　worldwide.　Inspired　by　the　specific　affinity　of　gefitinib　for　tumour　cells　and　the　strong　oxidation　capacity　of　singlet　oxygen,　we　combined　a　chemically　generated　singlet　oxygen　moiety　with　the　small-molecule　targeted　drug　gefitinib　to　improve　its　anticancer　effect.　We　designed　and　synthesised　a　novel　compound　(Y5-1),　in　which　a　small-molecule　targeted　therapy　agent　(gefitinib)　and　a　singlet　oxygen　(provided　by　an　in　vitro　photodynamic　reaction)　thermally　controlled　releasing　moiety　are　covalently　conjugated.　We　demonstrated　that　the　introduction　of　the　singlet　oxygen　thermally　controlled　releasing　moiety　enhanced　the　anticancer　activities　of　gefitinib.　The　results　of　this　study　are　expected　to　provide　a　novel　strategy　to　enhance　the　effect　of　chemotherapy　drugs　on　drug-resistant　cell　lines.　©　2020　Wiley-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim