The work aims to develop an ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method for determination of 4,4′-dihydroxybiphenyl migrated from polyphenylene sulfone feeding-bottles (PPSU) to provide test method basis of quality and safety of infant food packaging. The 50% (V/V) ethanol/water solution was chosen as food simulant to conduct the migration tests under testing conditions of (70 ℃, 2 h), and the analytes were separated on a C18 chromatographic column by gradient elution with a mobile phase consisting of deionized water and methyl alcohol. The qualitative and quantitative testing of 4,4′-dihydroxybiphenyl were carried out by multiple-reaction monitoring (MRM) collecting and scanning with electrospray ionization (ESI) source operating in the negative ionization mode, and external standard method was used for quantitative detection. Under the optimized conditions, there was a good linear relationship (with correlation coefficient R2>0.999 9) for the analyte in the concentration range of 5-200 µg/L. The limit of detection (LOD) and the limit of quantitation (LOQ) were 1.5 µg/L and 5 µg/L, respectively. The matrix effects of the method were in the range of 95.8%-114%, and the recovery range was 95.2% to 105%, and the relative standard deviation (RSD) was 1.0%-1.7% (n=6). This method is suitable for rapid determination of migration quantity of 4,4′-dihydroxybiphenyl in PPSU feeding-bottles, with the advantages of good accuracy and high sensitivity.