AIM:　To　understand　pharmacophore　properties　of　styrylquinoline　derivatives　and　to　design　inhibitors　of　HIV-1　integrase.　METHODS:　Comparative　molecular　field　analysis　(CoMFA)　was　performed　to　analyze　three-dimensional　quantitative　structure-activity　relationship　(3D-QSAR)　of　styrylquinoline　derivatives.　Thirty-eight　compounds　were　randomly　divided　into　a　training　set　of　28　compounds　and　a　test　set　of　10　compounds.　The　stability　of　3D-QSAR　models　was　proved　by　the　analysis　of　cross-validated　and　non-cross-validated　methods.　Moreover,　the　binding　mode　of　these　compounds　and　integrase　was　constructed　by　AutoDock　program.　RESULTS:　The　CoMFA　model　of　the　training　compounds　was　reasonably　predicted　with　cross-validated　coefficient　(q(2))　and　conventional　(r(2))　values　(up　to　0.696　and　0.754).　Then　the　model　was　validated　by　the　test　set.　The　resulting　CoMFA　maps　visualized　structural　requirements　for　the　biological　activity　of　these　inhibitors.　Docking　results　showed　that　a　carboxyl　group　at　C-7　and　a　hydroxyl　group　at　C-8　in　the　quinoline　subunit,　bound　closely　to　the　divalent　metal　cofactor　(Mg(2+))　around　the　integrase　catalytic　site.　Moreover,　there　is　a　linear　correlation　between　the　binding　energy　of　the　inhibitors　with　integrase　and　their　inhibitory　effect.　CONCLUSIONS:　The　present　study　indicated　that　the　CoMFA　model　together　with　docking　results　could　give　us　helpful　hints　for　drug　design　as　well　as　interpretation　of　the　binding　affinity　between　these　inhibitors　and　integrase.