Tyrosol (TYR, 2-(4-hydroxyphenyl)ethanol), one of the main phenols in olive oil and olive fruit, significantly strengthens resistance to thermal and oxidative stress in the nematode Caenorhabditis elegans and extends its lifespan. To elucidate the cellular functions regulated by TYR, we have used a proteomic procedure based on 2DE coupled with MS with the aim to identify the proteins differentially expressed in nematodes grown in a medium containing 250 μM TYR. After the comparison of the protein profiles from 250 μM TYR and from control, 28 protein spots were found to be altered in abundance (≥twofold). Analysis by MALDI-TOF/TOF and PMF allowed the unambiguous identification of 17 spots, corresponding to 13 different proteins. These proteins were as follows: vitellogenin-5, vitellogenin-2, bifunctional glyoxylate cycle protein, acyl CoA dehydrogenase-3, alcohol dehydrogenase 1, adenosylhomocysteinase, elongation factor 2, GTP-binding nuclear protein ran-1, HSP-4, protein ENPL-1 isoform b, vacuolar H ATPase 12, vacuolar H ATPase 13, GST 4. Western-blot analysis of yolk protein 170, ras-related nuclear protein, elongation factor 2, and vacuolar H ATPase H subunit supported the proteome evidence.