The microstructure evolution of AlCoCrFeNiTi 0.5 alloy and AlCoCrFeNiCu alloy during heat treatment was systematically studied, to reveal the influence rules of chemical activity of adding element on the microstructure evolution of AlCoCrFeNi system. Owing to the negative mixing enthalpy with the constituent elements, Ti element was mainly dissolved in the Al-Nirich phases, and aggravated the lattice distortion of B2 phase. The structure variation of BCC phase by adding Ti inhibited the formation of FCC phase and enhanced the precipitation of σ phase during heat treatment. Owing to the positive mixing enthalpy with constituent elements, Cu element tended to be repelled to the ID region and formed metastable Cu-rich FCC1 phase which would transform into Cu-Al-Ni-rich FCC2 phase with increasing temperature. The addition of Cu inhibited the precipitation of σ phase during heat treatment. Adding Ti maintained the stable dendritic morphology, while adding Cu reduced the thermal stability of microstructure. Two dramatic morphology changes occurred at 1000 °C and 1100 °C in the AlCoCrFeNiCu alloy. The lattice distortion of phase in AlCoCrFeNiTi 0.5 alloy was aggravated with increasing temperature up to 800 °C, then relaxed together with the dissolution of σ phase when temperature was above 900 °C. The variation in lattice distortion dominated the hardness of AlCoCrFeNiTi 0.5 alloy. With increasing heating temperature, the increasing volume fraction of region with FCC structure due to the transformation between FCC phases, and the pronounced coarsening in microstructure due to the reduced thermal stability, resulted in the mainly decreasing trend in the hardness of AlCo-CrFeNiCu alloy.