33 material specimens were tested to explore the mechanical properties of Q460 high-strength steel plate with holes under monotonic tension and low-cycle fatigue loadings. The stress-strain curve, skeleton curve and energy dissipation capacity comparison of the specimens were analyzed. The influence law of the design size of the specimen, the number of openings and the loading mode on the strength, stiffness, ductility and energy dissipation capacity of the specimens with holes were discussed. On this basis, a finite element model of specimen under fatigue loading was established by the ANSYS software to verify the correctness and reliability of the model. The test results showed that round holes have an adverse effect on the mechanical properties of specimens. The holes lead to stress concentration of specimens. Under the fatigue loads, increasing the number of axial holes of the specimens is beneficial to improve the ductility of specimen, but has an adverse effect on the energy dissipation capacity of the steel. Under low-cycle repeated loadings, the specimens usually cracked and destroyed near holes, and the failure shapes are saddle-shaped. The thickness of the specimens has a significant impact on the failure mode and mechanical properties of the high-strength steel. Under the fatigue loads, the damage forms of the opening specimens and the non-open tester are different, and two different fracture forms are exhibited as thickness. With the increase of the design thickness of the specimen, the fracture section shows two forms. With the increase of the thickness of the steel, the mechanical properties of the specimens have improved significantly. As the number of load cycles increases, the ductility of Q460 high-strength steel decreases and the energy consumption capacity increases.