In this study, CoMFA, CoMSIA and HQSAR techniques were used to study the important characteristic activities of thieno [2,3-d] pyrimidine derivatives for effective antitumor activity. The q² value of cross validation of CoMFA model was 0.621, and r² value of non-cross validation was 0.959. The best cross validation q² value of CoMSIA model was 0.522, while the r² value of non-cross validation was 0.961. The most effective HQSAR model was obtained by taking atoms and bonds as fragments: the q² value of cross validation is 0.535, the r² value of non-cross validation is 0.871, the standard error of prediction is 0.488, and the optimal hologram length is 199. The statistical parameters from the model show that the data fit well and have high prediction ability. In addition, molecular docking is used to study the binding requirements between ligands and receptor proteins, including several hydrogen bonds between thieno [2,3-d] pyrimidine and active site residues. The results obtained from these QSAR modeling studies can be used to design promising anticancer drugs.