The invention discloses a kind of niobium-titanium microalloying HRB400-scale screw-thread steel and a manufacturing method thereof. The screw-thread steel comprises C, Si, Mn, P, S, Nb, Ti, N and the balance Fe and impurities. The manufacturing method of the niobium-titanium microalloying HRB400-scale screw-thread steel comprises the following steps of smelting in a revolving furnace, treatment outside the furnace, continuous casting, casting blank heating and rolling. During smelting in the revolving furnace, alloy such as silicomanganese and ferroniobium is added for niobium microalloying treatment. During treatment outside the furnace, argon is blown in an argon station, and refining is conducted in an LF furnace. In the process of refining in the LF furnace, a ferrotitanium core-spun yarn is fed for titanium microalloying treatment. According to the technical scheme, before tapping, alloy such as silicomanganese and ferroniobium is added for niobium microalloying treatment, the ferrotitanium core-spun yarn is fed in the process of refining in the LF furnace for titanium microalloying treatment, after titanium is fused into molten steel, proper niobium-titanium microalloying treatment is conducted, the yield of the niobium-titanium alloy is increased, and stable, sustainable and low-cost production of the screw-thread steel is achieved.