The invention provides a preparation method of a titanium-steel composite plate with IF steel as an interlayer. The preparation method comprises the following steps of performing buffing and purging on the to-be-contacted surfaces of a blank, sequentially stacking a titanium plate, the IF steel interlayer and a substrate blank in the center, spraying the upper surface of the titanium plate with anisolating agent, and performing still standing for drying; aligning two groups of treated blanks, stacking the blanks together, and filling gaps between the substrate blanks with holding strips withthe same component; and performing vacuum drawing on a combined blank after blank combination, performing vacuum electron beam sealing welding, heating the treated combined blank to 880-920 DEG C, performing heat preservation, performing rolling at 860-900 DEG C, performing air cooling to a room temperature, and performing trimming, plate division and surface repair grinding to obtain the titanium-steel composite plate with a target thickness, wherein the reduction in a single pass is larger than or equal to 10 percent, and the total reduction is larger than or equal to 80 percent. The preparation method provided by the invention can improve the bonding capability and strength of a composite interface as well as the performance of a steel plate and the stability of the composite interfaceand can remarkably lower the production cost of the high-performance titanium-steel composite plate.