Effects of heat loss on the thermoacoustic instability simulation were studied based on flamelet-generated manifold (FGM) and large-eddy simulation (LES). The non-adiabatic and compressible LES-FGM model was conducted using a two-enthalpy-equation method. Two lean premixed CH4/air swirl flames, which were stable and unstable at phi = 0.6 and 0.8, respectively, were adopted. The velocity field, flame structure and acoustic pressure were measured using PIy, OH-PLIF and pressure sensors, respectively. For the stable flame, the nonadiabatic simulation predicts more accurately the reacting flow field and flame structure. For the unstable flame, the adiabatic simulation overpredicts the dominant frequency with an error of about 14 % but it reduces to only about 3.6 % with heat loss. The predicted adiabatic pressure amplitude is about two times the experimental result, but the error reduces to about 24 % with heat loss. Results suggested that the miss-predicted adiabatic frequency results from the over-predicted temperature. The over-predicted adiabatic pressure amplitude results from rapid reactant consumption, which makes the heat release rate (HRR) more in phase with the acoustic pressure. This work presents evident heat loss effects on the thermoacoustic instability, and the major underlying reasons are highlighted, which are essential to attain high-fidelity simulation of the instability.