• Damage of laser ablation can be minimized in the buffer gas condition of Helium, while the quality of LIBS spectra was improved. • Buffer gas jet was supplied in open atmosphere through a high-pressure gas cylinder instead of a vacuum target chamber, is more suitable for in-situ analysis. • The strategies performed in this work can also applied in other cultural heritage for the purpose of reducing LIBS damage. In this work, the potential of laser-induced breakdown spectroscopy (LIBS) on micro-destructive analysis of mural pigmented layers was studied under different buffer gases of air, Ar, N 2 , O 2 and He. In order to maintain the intrinsic advantages of LIBS for in-situ analysis, the buffer gas jet was supplied in open atmosphere through a high-pressure gas cylinder instead of a vacuum target chamber. Three kinds of red pigments, cinnabar, red lead, and red ochre that were widely used in Dunhuang murals, were utilized to prepare “mock-up” blocks. The effects of buffer gas on pigment discoloration, ablated crater, intensity of emission signal, signal-to-noise ratio (SNR) and stability of emission signal were studied. For practical application, the flow rates of buffer gas were optimized. It was found that the diameter of the ablated crater is the largest, the pigment discoloration around the crater is more serious in air after laser ablation, followed by Ar, N 2 , and O 2 . On the contrary, in buffer gas of He, these effects are the smallest. Moreover, Ar can enhance radiation of plasma to produce the strongest intensities of spectra, and He is the best choice for obtaining the best SNR and spectral stability among these buffer gases. The optimal gas flow rate for reducing damage and improving LIBS signal is around 5000cm 3 /min. In addition, the influence mechanism of different buffer gases on plasma was discussed qualitatively by combining the physical properties and plasma temperature. Finally, the buffer gas He was applied to analyze the actual mural fragments, and it was conclusively confirmed that He can reduce the damage to the pigment layer and the discoloration caused by high temperature in LIBS experiment.