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• Hydrocyclone-induced pretreatment for sludge disintegration was first proposed. • Efficient SCOD release was achieved at specific energy 0.18 W/g TS by hydrocyclone. • Combined pretreatment presents higher SCOD release, VFAs and CH 4 production. • Net profit of 131.73 USD/t TS was achieved for optimal combined pretreated sample. Hydrocyclone-induced pretreatment was first proposed for sludge disintegration to address excess sludge and to be served as a means of sustainable energy production. The effects of hydrocyclone disintegration alone and combination of hydrocyclone and alkaline pretreatments on sludge solubilization followed by anaerobic digestion were investigated. Initially, the flocs were disrupted through hydrocyclone at an optimal specific energy input of 0.18 W/g TS, with 2142 mg/L soluble chemical oxygen demand (SCOD) release. The hydrocyclone induced alkaline pretreatment in different sequence was investigated subsequently, and a maximal SCOD release of 4409 mg/L was observed in combination IV, which included hydrocyclone treatment throughout and alkaline treatment from 50th min to 80th min. Mechanisms of organics release via hydrocyclone-induced sludge pretreatment were also explored, and the sludge disintegration was attributed to its anisotropic flow field as well as common actions of sheared shedding and rotation desorption. The biodegradability analysis exhibited that the optimal combined pretreated sludge also exhibited 23.75% higher levels of VFA accumulation to 1017 mg/L, 32.38% more methane production to 134.29 mL CH 4 /g TS and 5.9% more VSS reduction to 29.3% relative to the hydrocyclone pretreated sludge. An economic of optimal combined sludge pretreatment offers a positive net profit of 130.42 USD/ton of TS, was assessed to be a cost-effective process. [ABSTRACT FROM AUTHOR]