The present invention provides a novel sewing-free hot melt adhesive TPU-PU leather and a preparation method thereof. The hot melt adhesive TPU-PU leather comprises a release paper, a hot melt adhesive film, a TPU film, and a dry PU film. The release paper comprises a bottom paper layer, an adhesive layer, a plastic layer, a transition layer, and a release layer; a hot melt adhesive raw material comprises polyester polyol, diisocyanate, polyether polyol, and a plurality of additives; a TPU raw material comprises polymer polybasic alcohol, 1,4-cyclohexane-diisocyanate, a chain extender, and a plurality of functional additives; and a PU raw material comprises polyester glycol, straight-chain diol, isocyanate, TDI Tripolymer, dimethylformamide, butanone, black sand, and a plurality of functional additives. According to the present invention, innovations are conducted on raw material components of the release paper, the hot melt adhesive, the TPU film, and the PU film; and the prepared sewing-free TPU-PU leather has the technical advantages of firm adhesion, durability, environmentally-friendly materials, no invisible harm to human body, and the like.