The invention provides a high-strength anti-fatigue steel and a manufacturing method for the steel, and pertains to the field of special steel and smelting of special steel. The method comprises adding proper amount Nb and Ti to carry out micro alloying, smelting by a combined blowing converter, LF refining, continuous casting the sheet blank, heating, removing scale by high-pressure water, hot rolling and laminar flow cooling, coiling, etc. and produces the high-strength anti-fatigue steel comprising by weight C% 0.07-0.13, Si% 0.15-0.35, Mn %1.0-1.3, P %<=0.025, S%<=0.010, Nb%0.015-0.020, Ti%0.010-0.025, Alt% 0.015-0.050, and the remainder Fe and trace foreign matters. The fatigue limit of the steel is up to 510 MPa, is of high strength, toughness and excellent forming performance, is applicable for manufacturing the longitudinal and cross beams in frames of load-carrying vehicles such as heavy and light duty trucks, etc.