Abstract: The system deviation of multi-collector thermal ionization mass spectrometry was researched, and the calibration techniques were established. The mass fractionation, multi-collector efficiency and the amplifier gain were calibrated by using isotope reference material and total evaporation technique, peak jumping technique, standard voltage and virtual amplifier technique, espectively. The new mathematical model for calibrating the nonlinearity of the amplifiers and ion count system was also established, and the calibration techniques were put forward. Based on these techniques, the isotope ratios can be measured accurately by multi-collector mass spectrometry.