Bone drilling process is the most prominent process in orthopedically surgeries and curing bone breakages. It is also very common in dentistry and bone sampling operations. Due to complexity of the material that is machined, bone, and the sensitivity of the process, bone drilling is one of the most important, common and sensitive processes in biomedical engineering field. The most critical problem which can occur during bone drilling is increasing the process temperature higher than allowable limit (47oC) which causes thermal necrosis or cell death in the bone tissue. In this study an empirical model is developed to able surgeon to predict the temperature of the process based on tool’s rotational speed, feed rate, tool diameter and effective interactions between these parameters. Experiments were designed and modeled using response surface methodology and to ascertain operation condition, optimization was performed. Results show that within the range of the investigated variables, with an increase in the tool diameter and cutting speed the rate of temperature increases. It is noted that the behavior of the feed rate is complex where in this paper is investigated precisely. Introduced response surface model is able to predict temperature behavior based on the input parameters. The allowable range of parameters in bone drilling operation is introduced to obtain a quick and swift a desirable operation.