To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4(+)-N and PO4(3-)-P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4(+)-N and PO4(3-)-P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4(+)-N and PO4(3-)-P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4(+)-N), pH > dosage > basicity (for PO4(3-)-P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.