To eliminate hazards during early phase of chemical process and obtain chemical reaction path with benign safety, the strategy is proposed by considering safety factors during reaction path synthesis. Material screening rules, safety constraints and inherent safety evaluation were integrated during reaction path synthesis. Safety factors were considered in this process. The implement of the strategy was divided into three steps. Based on inherent safety principles and indices, and reaction path including fire, explosion, toxicity hazards, material screening rules that considered safety were formed. According to material screening rules, the substance with extreme hazardous characteristics can be eliminated from materials. Focus on reaction hazards and substantial hazards, the NLP (non linear programming) model involving safety constraints was established. The result was shown that it was a more benign chemical reaction path. By inherent safety evaluation, the best relatively benign reaction path was obtained. Finally, by analyzing the application of reaction path synthesis for carbaryl production, the results were indicated that safety factors were considered during the early phase of process, and stoichiometric equations of chemical reaction path with benign safety were acquired. In conclusion, the strategy is useful in process decision-making.