The numerical investigations of interactions between a flame bubble with an incident shock wave (IW) and its focusing wave (FW) in a reactive CH 4 -O 2 -N 2 mixture are presented. The time-dependent, two-dimensional axisymmetric, reactive Navier-Stokes equations, with detailed chemical mechanisms, are employed to simulate the multiple shock-flame interactions process. The effects of the IW Mach number and chemical reactivity of mixture on flame structure and evolution are examined. The results of simulations show that the initial flame bubble can interact with IW, bow wave (BW), reflected BW, and FW in sequence. For the weak IW case, the repeated shock-flame interactions produce multiple Richtmyer-Meshkov (RM) instabilities that lead to the convolved flame with vortex structures, and the chemical heat release does not play a major role. While for the strong IW case, the multiple RM instabilities lead to the highly distorted flame with the complex vortices structures of large magnitude. With the lower reactive mixture, the instability process is the major mechanism for shock-flame interaction, while the chemistry only plays a minor role. However, with the higher reactive mixture, the distorted flame expands rapidly and finally forms the large-scale combustion through the interaction with FW. Both instability and chemical heat release play the important mechanisms in this case. The combustion acceleration in the highly reactive mixture can produce the stronger overpressure and the higher propagation speed of complex FW because of the chemi-acoustic interaction effect.