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To expand the diverse applications of wine lees and enhance the adhesive properties of its protein‐based adhesive, the supernatant of wine lees, separated using the alkali solubilization method, was combined with a small quantity of soybean protein as the raw material. Cross‐linking modification was then conducted using polyacrylamide polymers to prepare the protein‐based adhesive. The results indicated that a total mass fraction of 2.5 wt% NaOH and 3.0 wt% urea effectively stretched the protein structure. Additionally, a mass ratio of 4:10 of trimethylolpropane triglycidyl ether and acrylamide, under the action of the ammonium persulfate initiator, resulted in effective cross‐linking of polyacrylamide macromolecules. The addition of 7 wt% polyacrylamide macromolecules as a cross‐linking agent effectively facilitated the cross‐linking reaction with wine lees‐soy protein. After the cross‐linking modification, the surface of the adhesive became tight and smooth. As a result, the water‐resistance strength of the plywood increased from 0.2 to 1.27 MPa, marking a 635% enhancement, which significantly surpassed the standard for Class II plywood (GB/T 9846‐2015). [ABSTRACT FROM AUTHOR]