Fault-tolerant　control　(FTC)　has　been　developed　as　a　remedial　strategy,　which　can　take　action　with　fault　information　to　inhibit　the　occurrence　of　abnormal　condition,　such　as　sludge　bulking,　further　to　ensure　the　safety　and　stability　of　wastewater　treatment　process　(WWTP).　However,　since　the　coupling　relationship　among　fault　variables　results　in　the　complexity　and　obscurity　of　fault　characteristic,　especially　in　the　early　stage,　it　is　difficult　to　extract　the　available　fault　information　to　design　an　efficient　FTC.　Therefore,　to　tackle　this　issue,　a　knowledge-guided　fault-tolerant　compensation　control　(KG-FTCC)　with　fault　diagnosis　is　presented　in　this　article.　First,　a　knowledge　fault　diagnosis　strategy　is　employed　to　analyze　the　variable　causality　to　extract　the　root　fault　cause.　Then,　the　proposed　strategy　can　identify　the　fault　characteristic　with　coupling　relationship　to　assist　in　KG-FTCC.　Second,　a　knowledge　fault　compensation　mechanism,　which　can　leverage　the　fault　knowledge　and　data,　is　introduced　in　KG-FTCC　to　achieve　the　control　law　reconstruction.　Then,　the　proposed　KG-FTCC　can　catch　the　desired　set-point　to　suppress　the　sludge　bulking.　Third,　the　stability　of　KG-FTCC　is　proved　by　using　the　Lyapunov　theory.　Then,　the　effective　implementation　of　KG-FTCC　can　be　guaranteed.　Finally,　the　merit　of　KG-FTCC　is　verified　in　a　real　WWTP　and　a　simulation　application.　The　experimental　results　indicate　that　KG-FTCC　can　enhance　its　diagnosis　and　control　performance　to　ensure　the　safe　and　stable　operation　of　WWTP.