The Sino-US trade friction launched by the Trump government has evolved into “decoupling” in various fields such as science and technology, education and culture with China. After Biden took office, Trump government’s China policy was basically continued. The “decoupling” of the United States from China is different from previous small-scale economic and trade frictions. The fundamental reasons are the shift of the United States policy towards China, the periodic change of the status of a major power, the rise of the anti-globalization movement and populist movement in Western countries, and the prevention of China from seizing the historical opportunity of the Fourth Industrial Revolution. In the context of changes in the fundamental reasons for the “decoupling” of the United States from China, the initial conditions of the game between these two sides are very different from those in the past. It is necessary to scientifically and dynamically judge the trend of Sino-US economic and trade frictions and China’s optimal response based on the new background and realistic conditions. This paper attempts to analyze the above problems under the guidance of the two-tier game theory. Under the assumption of incomplete information, a two-tier dynamic game model is established. Taking this model as the analytical framework, this paper puts forward the possible trends of the game between China and the United States, and China’s different coping strategies and suggestions in the short and medium term and in the long term in the dynamic game environment. In the short and medium term, the target value of the United States to curb China’s right to high-quality development will not change. While responding accurately, China needs to reduce its dependence on the U. S. market and technology, further break the traditional dependence on the development path, rely on scientific and technological innovation to develop national competitiveness, and accelerate the formation of a domestic and international “double cycle” development pattern. In the long run, when the U. S. economy is affected by “decoupling”, the voice of the American people against “decoupling” grows, and due to the change of the target value of the United States to curb China’s right to high-quality development, China needs to adjust its response plan in real time according to the change of the U. S. policy of “decoupling”.