Experiment on suppressing fishbone activities is carried out in HL-2A tokamak by electron cyclotron resonance heating (ECRH). To achieve multiple deposition locations of ECRH, the magnetic field is in a range of 1.22–1.4 T from shot to shot. It is found that the fishbone modes exhibit different characteristics at different radial deposition locations. With the same injected power, the effect of off-axis ECRH is much better than that of on-axis heating. The fishbone modes can be completely suppressed when ECRH is deposited nearby the q= 1 rational surface, but would only mitigate in other cases. Further analysis indicate that injection of high power ECRH leads the electron temperature to increase, then the pressure gradient and plasma current density to change, finally safety factor to change and the minimum safety factor to reach a value larger than 1. Meanwhile, M3D-K simulation results show that the growth rate of fishbone mode declines with the increase of q _min. In other words, the growth of safety factor and disappearance of q= 1 rational surface induced by ECRH contribute to the suppression of fishbone activities. The experimental results reported here may not only help to better understand complex effects of ECRH on magnetohydrodynamic instability, but also provide a physics basis for actively controlling the energetic particle driven modes in the future magnetic confined fusion devices.