MRM→IDA→EPI→spectral library search model was used to establish a HPLC-electrospray ionization tandem mass spectrometry method for the multi-residue detection of fluoroquinolones in pig tissues. The quantitative and qualitative analysis of the target analyses were achieved by LC-MS/MS combining with spectral library search function. Tissue samples were extracted with N,N-Dimethylformamide and acetonitrile, purified with Waters HLB column，The analytical method in the present study was well validated and good results were obtained with respect to precision, repeatability and spiked recovery. The limit of detection of residues was 0.1~0.5μg/kg for fluoroquinolones, and with a linear range from 1.0 to 5000 μg/kg. The mean recovery was of 81.6%~114% and RSD was of 1.1%~11.2%.