The　gp41　inhibitors　were　selected　as　targets　to　investigate　the　interactions　between　gp41　inhibitors　and　the　structure　of　small　molecules　using　topomer　comparative　molecular　field　analysis　(CoMFA)　methods.　The　small　molecule　inhibitors　are　chosen　from　the　literatures,　and　the　molecule　model　was　constructed　by　using　Topomer　CoMFA.　Then,　the　predicative　ability　of　the　model　was　analyzed　according　to　the　statistical　method　and　an　ideal　prediction　model　is　obtained.　These　results　may　give　guidance　in　the　future　research　including　the　activity　prediction　of　the　compounds,　the　structure　modify　of　molecules,　and　drug　design.