In general, cell wall-degrading enzymes produced by plant pathogenic fungi are considered important pathogenicity factors. In this work, we evaluate the implication of xyloglucan endotransglucosylase/ hydrolase (XTHs), a potential hemicellulosic repairing enzyme, in the infection mechanism process by the fungus. This study investigated the SIXTHS expresion and xyloglucan endotransglucosylase (XET) activity during infection of two tomato fruit cultivars by Penicillium expansum Link. A. In infected fruits, XIET specific activity decreased drastically after long infection periods, 24 and 48 h for Canario and Money Maker tomato fruits, respectively. Real Time RT-PCR of eleven SIXTHS also showed a decrease in expression as the infection progressed in both tomato fruit cultivars. Results suggest that the reduction in SIXTHS expression during infection might be related with the fungus attack mechanism. We suggest a possible transcriptional control of the SIXTHS expression by the fungus, causing a decrease in XET activity and, consequently, lower xyloglucan endotransglucosylation, which changes the xyloglucan structure. These changes might increase the fruit softening and wall disassembly, facilitating the fungus colonization and the progress of the infection.