Abstract: In single-particle mass spectrometry analysis, particle-to-particle shift was observed during many ambient aerosol studies. Chemical information uncertainties would be introduced into data set during mass calibration of spectra if constant factors were used. The shifting scale of particle spectra was closely related to the vaporization/ionization laser spot size under typical ATOFMS operation conditions. A linear correlation between the mass deviation values and the actual m/z values was observed when spectrum was calibrated improperly. This paper details this problem from a theoretical point of view and proposes a new algorithm to calibrate every single particle’s mass spectrum with the optimized parameters.