The interest rate is always treated as the price of capital. It plays a most significant role in a country’s capital management and economic development, which poses a vital effect on capital market and monetary market. Therein, the commercial bank that is the important participants in the financial markets will be affected by the reform of interest rate liberalization. Before that, the deposits and loans rate are determined by the People’s Bank of China. Therefore, the People’s Bank of China has the unique authority to decide the magnitude of deposits and loans rate. Namely, the profitability of commercial Banks is denominated by the People’s Bank of China. As the interest rate liberalization, the profitability of commercial Banks will be inevitably impacted by it. Due to this, this paper tries to explore the operating mechanism between interest rate liberalization and profitability of commercial Banks. additionally, the total return to asset that represents the profitability of commercial banks; the net interest spread is treated as a measurement of interest rate liberalization. both are regarded as dependent variables. Meanwhile, the non-interest income or gross revenues and impaired loans or gross loans are treated as independent variables. In order to make the relation between them more clear, the sixteen representative listed commercial banks are divided into three categories (state-owned commercial banks, share-holding commercial banks and city-owned commercial banks) to conduct an empirical analysis. The findings indicate that 1% decrease in the net interest spread will result in 0.131% decrease in the profitability of state-owned in commercial banks, 0.399% decrease in the profitability of city-owned commercial banks and 0.201% decrease in the profitability of share-holding commercial banks. If the sixteen representative listed commercial banks are treated as a whole, 1% decrease in the net interest spread will lead to 0.246% in the profitability of all commercial banks.