In the present work, oxygen-free-copper (OFC) and Ti-6Al-4V (TC4) were joined by diffusion welding at first and then the structural control of the joint interface was mainly analyzed. It was found that firmly welded OFC/TC4 joint was obtained over a temperature range of 1023K~1103K, and the temperature played the key role which mainly affected the thickness of the joint interface. The results also showed that the joining of OFC to TC4 was attributed to the mutual diffusion effect of elements Cu and Ti. The structure of the joint interface was further controlled by exerting restrictive pressure (10MPa), controlling heating and cooling rates, lower welding temperature and reducing welding time etc. Finally, under certain welding parameters and by employing rational structural control techniques, well welded OFC/TC4 joint without large distortion or damage was obtained.