The traditional fluorescence detection method of PAEs is mainly the indirect fluorescence detection with bovine serum albumin (BSA). The 6 environmental priority control pollutants PAEs were taken as an example, and the 4th position on the benzene ring were introduced by substituent groups for molecular design to obtain PAEs derivatives with high fluorescence spectral intensity, which is advantageous for direct fluorescence detection. Simultaneously, the molecular docking method was used to simulate the binding of PAEs and BSA. The fluorescence intensities of PAEs after binding with BSA were calculated and compared with the fluorescence intensities of PAEs derivatives. The PAEs derivatives with significantly enhanced fluorescence spectra intensity were screened, which can provide theoretical support for the detection of PAEs derivatives. The results showed that 30 PAEs derivatives have been designed, and the fluorescence intensities of 18 PAEs derivatives were significantly increased by 100%～1850%, indicating that the intensities of the direct fluorescence detection of the PAEs derivatives are significantly stronger than those of the traditional fluorescence detection of the PAEs; the functional properties of the 18 PAEs derivatives (represented by stability and insulation) were less affected, and the environmental persistence values of the PAEs derivatives were reduced, and the bioconcentration values did not change significantly, and the mobility values and the toxicity values had different degrees of reduction. In addition, there is no interference between PAEs derivatives and other fluorescent substances (PAHs) (the minimum wave number difference is greater than the fluorescence detection resolution 0.30 nm), and the occupied orbital energies and the mulliken charge numbers are the main controlling factors that lead to the spectral characteristics of PAEs derivatives.