Biochemical effluents of pharmaceutical wastewater contain many humic substances and small amounts of suspended matter. In this study, foam fractionation coupled with heterogeneous Fenton (FF-HF) was designed as an advanced wastewater treatment process. Using the same settings based on separate optimizations, the dissolved organic matter (DOC) removal efficiency of FF-HF was 71.6 %, 23.7 % higher than that of HF alone. In addition, a shorter reaction time (37.3 % HF) and lower cost (31.6 % HF) were required for FF-HF. Thus, FF-HF is promising for the advanced treatment of pharmaceutical wastewater. According to the organic matter removal characterization, FF can effectively remove humic substances, organic colloids, and other macroscopic or hydrophobic organic matter. The design of the pre-FF process can decrease the pollutant load of HF, which explains the enhanced performance of the coupling process.