For determination of 18 photoinitiators (PIs) in paper packaging by gas chromatograph-mass spectrometry (GC-MS), a method with medium polar column (DB-624) was developed. The influences of carrier gas flow rate and column temperature on the separation performance of 18 PIs were studied. The results showed that the calibration curve of the GC-MS method indicated a good linear relationship, with R2 >0.99, the limits of detection range within 0.09~0.32 mg/m2, the limits of quantification range within 0.32~1.06 mg/m2, and the recoveries between 82.78%~114.03%, which proved that the method is feasible, accurate, and reliable.