Reducing production costs is one of the main objectives of process intensification; in this work, production costs of the distillation process are reduced by reducing equipment size and utility consumption from the perspective of process optimization to achieve the purpose of process intensification. The application of intelligent optimization algorithms in the optimization process of distillation is vital to achieving high efficiency and low costs. Combining the harmony search algorithm with the characteristics of distillation optimization, a new distillation harmony search algorithm (DHSA) was proposed, which includes the self-adaptive adjustment of parameters, roulette selection strategy, and ratio optimization strategy. Benefiting from the DHSA, the optimal total annual cost and calculation times were remarkably reduced when compared with reported algorithms in the optimization of four distillation cases including the two-column model, three-column model, reactive distillation column model, and dividing-wall extractive distillation column model. In addition, the highest coefficient of variation of DHSA in 10 parallel calculations is 1.25%. These results indicate that DHSA has the advantages of a higher-quality solution, less computing time, and higher stability, which not only improves the optimization efficiency and quality but also inspires the optimization strategies for other algorithms.