The inhibitory effect of caffeic acid on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was investigated in chemical model systems under microwave heating (MW). A mechanistic study was subsequently carried out to identify the inhibitory mechanism. The results showed that both for conductive heating (CV) and MW, the inhibition of PhIP increased with the concentration of caffeic acid but decreased with the prolongation of heating time. The inhibition on PhIP under MW was always higher than under CV, which were dominated by the difference in dielectric loss (ε″). UPLC-MS analysis showed that caffeic acid releases a CO2 molecule to produce 4-vinylcatechol which can form adducts with phenylacetaldehyde, thus reducing its availability for PhIP formation. The structure of adduct was characterized as 3-(3,4-dihydroxyphenyl)-2-phenylbutanal with a molecular weight of 256. The findings indicate that trapping of phenylacetaldehyde by 4-vinylcatechol is a key mechanism of caffeic acid in inhibiting PhIP formation.