The lipid profiles of the truffles with different treatments were determined by ultra-high-performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-QE Orbitrap/MS/MS) and the volatile organic compounds (VOCs) were identified by purge-and-trap-gas chromatography-mass spectrometry (P&T-GC–MS). A total of 37 lipid molecular species and 28 VOCs were tentatively identified. Lysophophatidylcholine (LPC), triacylglycerol (TG) and sphingomyelin (SM) in heat-drying truffles, phosphatidic acid (PA) in freeze-drying and fresh truffles might be the key lipids that bound VOCs. Furthermore, the correlation between lipids and VOCs were analyzed by 19 differential lipids and 7 VOCs. The findings indicated that TG 18:2/18:2/18:2 and Cardiolipin (CL) 16:0/16:0/18:2/18:2 might be the key lipid molecule species for the formation of 2-methoxyphenol. The study helps to understand the effect of different treatments on the lipid profiles and provides the mechanistic insights to the relationship between the lipids and VOCs of truffles.