Given the low reaeration efficiency of fine pore aeration system in rivers, the oxygen mass transfer coefficient was used as the evaluation index to study effects of five factors, including the pore diameter of a fine pore aerator, aeration depth, salinity, and the mass concentrations of BOD5 and sodium dodecyl benzene sulfonate (SDBS), on the oxygenation performance based on single factor test and response surface optimization test. Also, a multiple quadratic regression model was established to optimize aeration parameters. The results show that all of the five factors can affect the oxygen mass transfer coefficient, and the order of factor significance is as follows: aeration depth, the mass concentration of SDBS, salinity, pore diameter, and the mass concentration of BOD5. In addition, there is a remarkable interaction between the mass concentration of SDBS and pore diameter or salinity. With reasonable error between model prediction and experimental results, the regression model is accurate and reliable.