The effects of density ratio and differential diffusion on premixed flame propagation of H2/O2/N2 mixtures are investigated by constant volume combustion chamber. The density ratio and differential diffusion are controlled independently by adjusting the O2/N2 ratio and equivalence ratio. Results show that the density ratio has no effect on turbulent burning velocity while the differential diffusion has a promotion effect on turbulent burning velocity. The onsets of laminar flame acceleration are promoted by both density ratio and differential ratio. The turbulent flames perform a continuous acceleration propagation and the dependence between flame propagation speed and flame radius can be characterized as (dR/dt)/(σ·SL) ∼ R0.33∼0.37, which is lower than the 1/2 power law. The acceleration parameters of laminar flames and turbulent flames (u’/SL = 1) are around 0.17 and 0.36 respectively, and both of them are not affected by density ratio and differential diffusion. The empirical formula m = 0.19·(u’/SL)0.4+0.17 is concluded to quantitatively describe the accelerative characteristics of laminar and turbulent flames. The current study indicates that the acceleration of laminar flames is mainly induced by flame intrinsic instability, and the latter can affect the acceleration onset but not affect the fractal excess. The acceleration of turbulent flames is dominated by turbulent stretch, while the effects of density ratio and differential diffusion can be ignored.