MLSS and SRT are key parameters in process control. A full-scale modified A2/O process varying with MLSS and SRT was evaluated, and MLSS and SRT effect was distinguished by statistical methods so as to seek early diagnosis and efficient control. Results showed that complete SRT rather than MLSS resulted in considerable effluent SS fluctuation with inert SS accumulation. COD removal was more sensitive to MLSS than SRT. Increasing MLSS until 2,000 mg/L could improve COD, SS, and NH3 removal efficiency, and further increases in MLSS simply enhance stability. MLSS of 2,000 mg/L was also efficient in TP removal. SRT shorter than 30 d was the guarantee for PAOs, while SRT longer than 90 d was equal to complete SRT as TP was removed by assimilation. Prolonged SRT from 30 to 90 days reduced the Yobs from 0.17 to 0.15 g MLSS/g COD. MLSS and SRT had no effect on TN removal. Correlation between MLSS and influent was effective for diagnosing longer SRT. MLSS/RSS could be an indicator for TP removal. The suggested control strategy was SRT-assisted MLSS control.