This study examined the effects of different doses of irradiation treatments on protein structure and digestion characteristic of seed-watermelon seed kernel protein. The results showed that, the molecular structure of seed-watermelon kernel protein was unfolded after the irradiation treatment, the content of beta-sheet structure in the secondary structure was decreased, while the content of random coil structure increased. The average particle size of the protein increased, and the hydrophobic group buried in the beta-sheet structure was exposed hence the surface hydrophobicity increased. Besides, the surface morphology of seed-watermelon protein changed from smooth and flat to coarse and concave, the specific surface area in contact with the aqueous medium increased and its solubility increased, the distribution of peptides in the digesta became wider, and the small molecular weight peptides gradually increased.