Bactrocera dorsalis (Hendel) is a fruit-eating pest that causes substantial economic damage to the fresh produce industry in tropical and sub-tropical countries. Methyl eugenol (ME) is a powerful attractant for mature males of B. dorsalis, and has been widely used for detecting, luring and eradicating B. dorsalis populations worldwide. However, the molecular mechanism underlying the olfactory perception of ME remains largely unknown. Here, we analyzed the differential proteomics profiling of the antennae between ME-responsive and ME-non-responsive males by using isobaric tags for relative and absolute quantitation (iTRAQ). In total, 4622 proteins were identified, of which 277 proteins were significant differentially expressed, with 192 up-regulated and 85 down-regulated in responsive male antennae. Quantitative real-time PCR (qRT-PCR) analysis confirmed the authenticity and accuracy of the proteomic analysis. Based on the iTRAQ and qRT-PCR results, we found that the odorant-binding protein 2 (BdorOBP2) was abundantly expressed in responsive male antennae. Moreover, BdorOBP2 was significantly up-regulated by ME in male antennae. Mature males showed significantly greater taxis toward ME than did mature females. Silencing BdorOBP2 reduced mature males' responsiveness to ME. These results indicate that BdorOBP2 may play an essential role in the molecular mechanism underlying B. dorsalis olfactory perception of ME.