A series of waterborne polyurethane (WPU) products were prepared by prepolymer dispersion method using isophorone diisocyanate (IPDI) , propylene oxide (PPG) , trimethylolpropane (TMP) , dihydromethylic acid (DMPA) etc. The effects of neutralization degree, isocyanate index (R value), amount of hydrophilic agent and crosslinking agent on water resistance and mechanical properties of WPU were studied. The results showed that the tensile strength and water absorption increased with the increase of neutralization degree. With the increase of R value, the tensile strength increased and water absorption decreased. The tensile strength and water absorption of the film increased with the increase of the dosage of hydrophilic agent. With the increase of the dosage of cross-linking agent, the tensile strength of the film first increased and then decreased, and the water absorption first decreased and then increased. The results of orthogonal test show that the order of factors affecting WPU film water absorption is: DMPA dosage>R value>TMP dosage>neutralization degree. When the neutralization degree is 80%, the dosage of TMP is 1%, the dosage of DMPA is 4%, and the R value is 1.10, the WPU film has the lowest water absorption (8.72%) and the best water resistance. The order of factors affecting film tensile strength is: DMPA dosage>TMP dosage>R value>neutralization degree. When the neutralization degree is 90%, the dosage of TMP is 3%, the dosage of DMPA is 5%, and the R value is 1.20, the tensile strength of WPU film is the highest (12.35 MPa).