In this study, the infrared (IR) and Raman spectra of 28 kinds of fentanyl-class substances were analyzed. The spectrum characteristics and the distinguishing ability of IR and Raman for fentanyl-class substances were investigated. On the whole, IR and Raman spectra of fentanyl compounds showed different spectral characteristics and were complementary. For IRspectroscopy, different salt forms of fentanyl-class substances showed significant differences in the range of 3200~2 000 cm^-1. The base-form compounds showed strong absorption peaks at 2 972~2 952 cm^-1, the hydrochloride compounds showed multiple absorption peaks with medium intensity at 2 600~2 320 cm^-1, and the citric acid compounds showed broad absorption peaks with moderate intensity at 3 100~2 800 cm^-1. In addition, the IR spectra all showed a strong absorption peak caused by the stretching vibration of C=O bond at 1 750~1 630 cm^-1, and a strong single or double peaks caused by the bending vibration of the benzene ring at 710~680 cm^-1. For Raman, all types of fentanyl-class substances showed a strong Raman peak at 1 001~1 002 cm^-1, which was caused by the in-plane bending vibration of C—H bond on the benzene ring. In the Raman spectra of substituted compounds containing alkyl, phenyl and tetrahydrofuran groups, the peak at about 1 000 cm^-1 was the base peak, and the intensity of other peaks was all lower than 30% of the base peak. For Raman spectra of substituted compounds containing fluorine, furan and sulphur groups, there were other high-intensity peaks besides the base peak at about 1 000 cm^-1. IR spectrum can distinguish all fentanyl-class substances, even for certain structural analogues with high spectrum similarity. When there is no fluorescence interference, Raman spectra are distinguishable for all fentanyl-class substances. The Raman spectra for homologues with differences in only a methyl group and regioisomers with methyl substituted at different positions were found to be highly similar; however, their spectra demonstrated small but detectable differences. Both the Infrared and Raman methods were simpler, more rapid, less expensive, non-destructive, and fit for in-field testing. Raman may be used non-invasively, minimizing exposure to potentially dangerous substances; however, its fluorescence based problem sometimes affects its usefulness. Compared with Raman, IR shows no fluorescence interference, higher spectrum consistency, and a more complete commercial spectrum library, which is the preferred method for rapid qualitative analysis of fentanyl-class substances in-field.