Cancer　immunotherapy　has　achieved　a　leap　from　the　laboratory　to　the　clinic,　especially　for　therapeutic　applications　based　on　programmed　cell　death-1　(PD-1)　and　its　ligand　(PD-L1)　that　target　tumour　immune　escape　and　growth.　At　present,　13　PD-1/PD-L1　monoclonal　antibodies　(mAbs)　have　been　approved　as　PD-1/PD-L1　inhibitors　by　the　United　States　Food　and　Drug　Administration　(FDA).　However,　inherent　limitations　of　mAbs,　including　poor　bioavailability　and　immunogenicity,　have　led　researchers　to　pursue　alternatives　and　develop　small-molecule　inhibitors　with　low　molecular　weight.　Biphenyl　derivatives　are　small-molecule　inhibitors　of　PD-1/PD-L1　with　advantages　of　oral　bioavailability,　high　tumour　penetration　and　better　pharmacokinetic　properties.　In　this　work,　we　review　progress　and　structure-activity　relationship　analysis　of　biphenyl　derivatives　as　PD-1/PD-L1　inhibitors.　The　conclusions　could　contribute　to　the　design　of　PD-1/PD-L1　inhibitor　candidates　for　cancer　immunotherapy.　©　2023,　The　Author(s),　under　exclusive　licence　to　Springer　Science+Business　Media,　LLC,　part　of　Springer　Nature.