Non-steroidal anti-inflammatory drugs (NSAID’s) are considered one of the most commonly prescribed drugs all over. The most recent and powerful NSAID’s are COX-II inhibitors; which are clinically effective antiinflammatory agents with less gastrointestinal and renal toxicity, yet they had serious side effects like myocardial infarction. Therefore, there is still a need to develop better therapeutically effective and tolerable COX-II inhibitors. In this study, screening of various 2,3-disubstituted-4(3H)-quinazolinones, using the Molsoft ICM 3.5; a docking software; against the COX-II enzyme is reported. Various molecular structures of ligands were docked and scored to identify structurally similar ligands to celecoxib (reference ligand) in binding interaction to COX-II binding site. The results show that 2,3-disubstituted-4(3H)-quinazolinones moiety with cyclohexyl at C-2, and aryl moiety at N-3 binds directly or indirectly to the ring system with high binding affinity. The docked ligand has orientations completely different from that of the reference drug celecoxib.