The microstructure of TC18 titanium alloy die forging shows delamination. The brighter microstructure has lower performance and is often called cold die microstructure (CDM). Decreasing the cooling rate can hinder the generation of CDM, but it may also aggravate the die wear. The balance relation between microstructure delamination of TC18 frame forging and the die wear in different parameters was studied by simulation and experiment. The programs to predict the CDM and wear depth were built and realized by secondary development. Continuous forging production process was simulated by DEFORM software and the characteristics of CDM and wear were researched. The balance relationship between the die wear and the CDM content in different parameters was discussed by the response surface method and the optimal parameters. Results show that the preheating temperature of die plays a dominant role in the variation of the wear depth. The most influential factor of CDM content is the contact condition. Applying glass fiber can reduce the CDM content without increasing the wear depth.