In the process of HIV-1 virus replication, integrase plays a quite important role. Integrase inhibitors of quinoline ring derivatives were analysed by the Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Induces Analysis (CoMSIA) and Topomer CoMFA methods. Firstly, 77 compounds were selected to form the training and test sets. Secondly, predictive models were constructed with the CoMFA, CoMSIA and Topomer CoMFA methods. The CoMFA model yielded the best model with q (2) of 0.76 and [Formula: see text] of 0.99, the CoMSIA model has q (2 )= 0.70 and [Formula: see text] of 0.99, while the Topomer CoMFA model has q (2) of 0.66 and [Formula: see text] of 0.97. These results provide a helpful contribution to the design of novel highly active HIV-1 integrase inhibitors.