Tropomysin receptor kinase A (TrkA) is an excellent drug target for its important roles in pain sensation as well as tumour cell growth. Up to now, the discovered TrkA inhibitors belong mostly to type-I class targeting the ATP binding site, while we aim to find type-II inhibitors because they are deemed to have improved kinase selectivity and slower off-rates than their counterparts. The type-II inhibitors can induce TrkA in an inactive DFG-out form and insert in an additional hydrophobic cavity adjacent to the ATP binding pocket. The current article describes efforts to discover novel type-II scaffolds against TrkA via integrating pharmacophore-based 3D-QSAR modeling, database screening and molecular docking. The robustness of the best model, AAHRR.8, was seriously ascertained by the high R2 (0.9027), Q2 (0.7048), low RMSE (0.4016) and SD (0.3635). It was further used as a 3D query to screen against our in-house collection of almost 1.3 million compounds followed by molecular docking simulations using three docking protocols involving Glide SP, Surflex and Glide XP. 12 hits, which mapped well on the best pharmacophore model, displayed good docking score and rational binding mode, were selected as promising selective leads of TrkA. Finally, ADME study was carried out and the results indicated that these 12 compounds own drug-like properties. The 12 hits together with the best 3D-QSAR model will be helpful for future potent TrkA agent development.