On August 18, 2017, the office of the U.S. trade representative announced to initiate 301 investigation towards China. In order to predict the trend of 301 investigation, the paper tries to analyze the "301 investigation" towards China by using the method of historical comparison, and concluded that all the 301investigation were resolved in the form of negotiation although each one has its own background and process. Then, the paper analyzes the realistic rationality of the negotiation between China and the United States in the "301 investigation" with game theory, and predicts that the solution of 301 investigation in 2017 will eventually be resolved by negotiation or resort to WTO dispute settlement procedure. Finally, the paper puts forward the policy suggestions from negotiation, retaliation and WTO framework.