In this study, mixed-integer hybrid differential evolution is applied to solve the synthesis problems of the nonsharp distillation sequence and heat exchanger network. A general mixed-integer nonlinear programming (MINLP) model is proposed to formulate the superstructure of the distillation sequence problem. The proposed MINLP model is more suitable for use with an evolutionary algorithm. We introduce mixed-integer hybrid differential evolution along with a multiplier updating method, including adaptive penalty parameters (MIHDE-MUM-APP), to solve constrained synthesis problems. Computational examples reveal that nearly identical minimum solutions can be obtained using MIHDE-MUM-APP even under wide variation of the initial penalty parameters.