Cancer is a major cause of death worldwide. Small molecule inhibitors have become a major therapeutic treatment for cancer. In this study, a series of novel 4-(pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide derivatives were designed, synthesized and evaluated for their antitumor activity against the A549, Hela and MCF-7 cell lines. Among them, the optimal compound 35 was found to possess excellent inhibitory activity against the A549, Hela and MCF-7 cell lines with IC values of 5.29 ± 0.58, 3.72 ± 0.91, and 9.23 ± 0.56 μM, which were superior to Golvatinib. The structure-activity relationship showed that the introduction of 7H-pyrrolo[2,3-d]pyrimidine along with the F atom of the central and terminal benzene was beneficial to the improvement of inhibitory activity of the target compounds. Besides, we took further study on the combined mode between compound 35 and c-Met kinase through molecular docking.