We extends our previous works on analytical excited-state energy Hessian within the framework of time-dependent density functional theory(TDDFT)to couple with molecular mechanics(MM).The formalism,implementation,and applications of analytical first and second energy derivatives of TDDFT/MM excited state with respect to the nuclear and electric perturbations are presented.Their performances are demonstrated by the calculations of adiabatic excitation energies,and excited-state geometries,harmonic vibrational frequencies,and infrared intensities for a number of benchmark systems.The consistent results with the full quantum mechanical method and other hybrid theoretical methods indicate the reliability of the current numerical implementation of developed algorithms.The computational accuracy and efficiency of the current analytical approach are also checked and the computational efficient strategies are suggested to speed up the calculations of complex systems with many MM degrees of freedom.Finally,we apply the current analytical approach in TDDFT/MM to a realistic system,a red fluorescent protein chromophore together with part of its nearby protein matrix.The calculated results indicate that the rearrangement of the hydrogen bond interactions between the chromophore and the protein matrix is responsible for the large Stokes shift.To capture polarization effects in excited states,we are combining our approach with polarizable QM/MM approaches based on the induced dipole model.