: In order to systemically evaluate the reliability of the method of predicting ionization energy with density functional method in quantum chemistry [B3LYP/6-311++G(d,p)] and composite ab initio (G3B3), 70 chemical portions of known ionization energy in cigarette smoke were calculated and analyzed as the validation set, and some smoke portions of unknown ionization energy were calculated. Meanwhile, by synchrotron radiation photoionization mass spectrometry assisted with an in-house cigarette smoke sampler, the gas phase components in cigarette smoke were on-line analyzed. The photoionization mass spectra and photoionization efficiency spectra were measured, also obtained were the experimental values of the ionization energy of some smoke portions. The results showed that G3B3 method was competent for calculating ionization energy of various smoke portions, the accuracy was up to 0.06 eV, and the calculated results were suitable for the qualitative analysis of cigarette smoke components.