HIV-1 integrase (IN) is an important drug target of current anti-AIDS research and drug development. The drug resistance mutations (DRMs) are the main reason of integrase inhibitor therapy failure, but the drug resistance mechanism remains unclear. We introduced mutations artificially into HIV-1 integrase, tested the activity and drug resistance of individual mutations, and analyzed the integrase drug resistance mechanism preliminarily. The mutations involved contain two single mutations, E92A and N155S, and a double mutation, E92A/N155S. These mutations were obtained using genetic engineering methods, and these recombinant proteins were prepared after prokaryotic expression and protein purification. The strand-transfer activity of the integrases was tested by a magnetic beads based ELISA. S-1360 and Raltegravir were used for drug resistance testing. Besides, molecular docking was performed to study the complex of S-1360 and HIV-1 integrase central catalytic domain (including wild type and mutated type) using Autodock. The main results are as follows: N155S mutation decreases about 80% of the integrase strand transfer activity, while E92A/N155S only decreases about 42%. It indicates that, the E92A mutation on the base of N155S mutation increased the integrase activity observably. Besides, E92A and E92A/N155S mutations exhibit different drug resistance to different inhibitors, and they are more resistant to Raltegravir than to S-1360. A mutation could cause structural change of the integrase catalytic center domain, and the structural change eventually influences the activity and drug resistance. As to E92A, it may reduce the electrostatic interaction to the amino acids around it, and influences D64 and D116 indirectly, which are key amino acids of catalytic center domain. This may give a rational explanation to activity recovery of N155S caused by E92A.