Table grapes are one of the most common fruits throughout the world. Decay of grapes caused by pathogenic fungal infections results in tremendous economic losses. The aim of this study was to evaluate the effect of Yarrowia lipolytica on the control of postharvest decay of grapes caused by Penicillium rubens and the possible mechanisms involved. The results showed that Y. lipolytica provided significant inhibition of the postharvest decay of grapes by P. rubens compared with the control. When the concentration of Y. lipolytica was 1 x 10(9) cells/mL, decay incidence and decay diameter of grapes were 12.45% and 6.19 mm, respectively. Y. lipolytica reduced spore germination and germ tube length of P. rubens. Moreover, the results also showed that the activities of defense-related enzymes, including polyphenoloxidase (PPO), peroxidase (POD), catalase (CAT), phenylalanine ammonialyase (PAL), ascorbate peroxidase (APX) and beta-1,3 glucanase (GLU),were significantly enhanced in grapes treated with Y. lipolytica. Similarly, the expression levels of these genes were also increased in grape fruits treated with Y. lipolytica. The results suggested that the possible resistance mechanism of Y. lipolytica was to enhance the defense-related enzymes and genes, ultimately reduce postharvest decay caused by P. rubens in grapes. Altogether, the research work confirmed that Y. lipolytica has potential biocontrol efficacy and could be used as a biocontrol agent to prevent the postharvest decay of grape fruits.