Abstract: The nonlinearity of the Faraday detector’s amplifiers of a thermal ionization mass spectrometer (TIMS) was investigated，and the mathematical model of calibration was built. Using the model, a kind of isotopic reference material could be used to calibrate the nonlinearity of the Faraday detector’s amplifiers, directly. Correspondingly, a series of isotopic reference materials must be used to calibrate the nonlinearity, generally. The nonlinearity of the Faraday detector’s amplifiers of a thermal ionization mass spectrometer was researched by UTB-500 uranium isotope reference material and peak-jumping mass spectrometry measurement technique. The results show that the nonlinearity can be calibrated, commendably. Furthermore, the experiment proves that the factor of the nonlinearity is constant at fixed isotopic ratio, and the factor is unchangeable at variation ion current.