The mass spectrometry analysis of oxygenated volatile organic compounds (OVOCs) remains challenging due to their limited ionization efficiencies. In this study, we surprisingly found that, under vacuum-UV (VUV) excitation, a gaseous mixture of CH2Cl2/H2O/analyte (OVOCs) in N2 buffer generated large amounts of H3O+ and protonated analyte even when the photon energy was lower than the ionization energy of the neutral species involved. In contrast to those obtained with VUV photoionization alone, the signal intensities of oxygenated organics can be amplified by more than 3 orders of magnitude. The isotope tracing experiment revealed that the proton donor is water, and the dependence of the signal intensities on the VUV photon intensities verified that the reaction was a single-photon process. The observed ionization process is assigned as an undocumented chemi-ionization reaction in which a complex formed from the ion-pair state CH2Cl2*, H2O, and analyte and then autoionized to produce the protonated analyte with the aid of the reorganization energy released from the formation of CH2O and HCl. Essentially, here we present an efficient chemi-ionization method for the direct protonation of oxygenated organics. By the method, the mass spectrometric sensitivities toward acetic acid, ethanol, aldehyde, diethyl ether, and acetone were determined to be 224 ± 17, 245 ± 5, 477 ± 14, 679 ± 11, and 684 ± 6 counts pptv-1, respectively, in 10 s acquisition time. In addition, the present ionization process provides a new method for the generation of a high-intensity H3O+ source (∼1011 ions s-1, measured by ion current) by which general organics can be indirectly protonated via a conventional proton-transfer reaction. These results open new aspects of chemi-ionization reactions and offer new technological applications that have the potential to greatly improve mass spectrometry sensitivity for detecting trace gaseous organics.