A high-strength fatigue-proof steel and a manufacture method thereof belong to the field of special steel and smelting technology thereof. The high-strength fatigue-proof steel comprises, by weight percentage, C 0.07 to 0.13%, Si 0.15 to 0.35%, Mn 1.0 to 1.3%, P not larger than 0.025%, Si not larger than 0.010%, Nb 0.015 to 0.020%, Ti 0.010 to 0.025, Al 0.015 to 0.50t%, and Fe and trace amount of impurities allowance. The high-strength fatigue-proof steel can be manufactured by adding a proper amount of Nb and Ti elements, micro-alloying, smelting by a combined-blown converter, LF refining, slab continuous casting, heating, high-pressure water descaling, continuous hot rolling, laminar cooling and reeling. The steel has a fatigue limit up to 529 MPa, high strength, high roughness and good forming performance, and is used for manufacturing stringer, beam, etc. of the frame of heavy vehicles such as heavy trucks and light trucks.