The pyromorphite in Guilin, Guangxi, has bright colors and complete crystals, favored by mineral and gem collectors. In this paper, six pyromorphite samples from Guilin and Guangxi with different colors were selected. The samples chemical composition and vibration spectrum were tested by energy-dispersive X-ray fluorescence spectrometer, infrared spectrometer, Raman spectrometer, and X-ray powder diffractometer to explore the relationship between the vibration spectrum and the chemical composition (isomorphism) and crystal structure. The results show that the main chemical element of the samples is Pb, followed by P and Cl. The mid-infrared and Raman spectra mainly characterize the bending and stretching vibrations of PO3-4, in which the bands below 300 cm-1 are related to the lattice vibration. The antisymmetric stretching vibration of AsO3-4 is visible at 882/822 cm-1, and the CO2-3 vibration is related at 1 461 cm-1, indicating that CO2-3 and AsO3-4 replace a small amount of PO3-4 in the structure of Guangxi Guilin pyromorphite. Near-infrared spectroscopy tests show spectral bands related to transition metal ions Fe2+and Cu2+ in the sample, indicating that Fe2+and Cu2+ may simultaneously replace Pb2+ and exist in the crystal structure. The 4 000~8 000 cm-1 region mainly displays phosphate ions, arsenate ions, and their overtone and combination tones, as well as the overtone and combination tones of water molecules, hydroxyl groups, hydroxyl, and metal ions. It is confirmed that crystal, structural, and adsorption water are in the sample, with the channel ion Cl partially replaced by OH. The results of the comprehensive analysis of mid-infrared, near-infrared, and Raman spectra show a wide range of isomorphism in the samples of pyromorphite in Guilin, Guangxi. This phenomenon leads to a decrease in the symmetry of phosphate ions, a distortion of the structure, and a splitting and displacement of the spectral band. Meanwhile, X-ray powder diffraction shows that isomorphism has little effect on the cell parameters a0 and b0, while c0 fluctuates within a small range.