Up-conversion　nanoparticles　(UCNPs),　especially　single-band　bright　red　UCNPs,　have　better　penetration　of　biological　tissues,　absorb　less　lost　energy,　and　have　higher　sensitivity　and　accuracy　in　the　determination　of　actual　biological　samples　in　the　field　of　biosensing.　Here,　a　novel　colorimetric　and　fluorescent　dual-channel　method　based　upon　an　internal　filtration　effect　(IFE)　quenching　mechanism　was　proposed　for　the　quantitative　analysis　of　xanthine　(XA)　by　using　red　UCNPs　as　fluorescence　indicator　and　3,3′,5,5′　-tetramethylbenzidine　(TMB)　as　chromogenic　substrate.　The　sensitivity　of　the　detection　system　was　also　enhanced　by　a　cycle　signal　amplification　strategy　based　on　the　Fenton　reaction.　Under　the　best　conditions,　the　detection　limits　of　XA　by　fluorescent　and　colorimetric　methods　were　0.58　μM　and　1.19　μM,　respectively.　The　developed　method　was　applied　to　the　detection　of　XA　in　actual　serum　samples,　and　the　recoveries　of　the　spiked　samples　by　fluorescent　and　colorimetric　methods　were　in　the　range　of　96.3–104.3　%　and　94.3–105.4　%,　respectively.　In　addition,　the　commercial　ELISA　method　was　used　to　verify　the　application　of　the　proposed　method　and　the　test　results　of　XA　were　close　to　those　obtained　by　fluorescent　and　colorimetric　methods,　indicating　that　the　accuracy　of　the　developed　nanosensing　system　was　acceptable.　©　2023　Elsevier　B.V.