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To further elucidate the molecular mechanism of the germination in common wheat, a differential proteomic analysis was completed between the F1 hybrid RS5322 and its parental lines (RS53 and SN22) using isobaric tags for relative and absolute quantitation (iTRAQ) based strategy. Rapid grain germination and superior young seedling growth were observed in the F1 hybrid line. A total of 807 differentially abundant proteins (DAPs) were identified by iTRAQ analysis of grains at 48 h after imbibition in distilled water. Bioinformatics analysis shows that 638 DAPs were annotated in 38 Gene Ontology functional groups, 764 DAPs were classified into 23 clusters of orthologous groups of protein categories, and 538 DAPs were enriched in 65 Kyoto encyclopedia of genes and genomes pathways. Real time quantitative PCR of 12 genes encoding different important proteins showed certain transcriptional and translational expression similarities during grain development. In the F1 hybrid, the DAPs were particularly those involved in starch and sugar metabolism, protein metabolism, protein modification, and ubiquitin proteasome system (UPS). It was speculated that UPS might be responsible for a high germination ability in the F1 hybrid by regulating storage substance metabolism. The DAPs identified in this study provide a scope for improving the grain germination trait in agricultural crops.