Lysozyme has been identified as a promising approach for enhancing waste activated sludge (WAS) anaerobic fermentation. However, the extracellular polymeric substance (EPS), functioning as a ‘protective shell’ for microbial cells, hindered the lysozyme transfer and subsequent interaction with cell wall, resulting in excessive dosage and limited efficiency in practical engineering applications. This study innovatively proposed a sodium pyrophosphate (SP) assisted lysozyme treatment, aiming to overcome such limitations and enhance the solubilization and hydrolysis efficiency. As a result, 3583.5 mg COD/L short-chain fatty acids (SCFAs) and 23.1 % acidification rate were achieved after 2-day anaerobic fermentation within SP-lysozyme treatment. Mechanism investigation revealed that SP facilitated EPS disruption by inducing a loosening of the protein structure, leading to the enhanced solubilization of organic matter within the EPS and microbial cells. Consequently, the release of substantial substrates contributed to the enrichment of functional microbes associated with hydrolysis and acidogenesis, accompanied by the augmentation of corresponding metabolic functions. Besides, the key functional genes analysis demonstrated the amino acid metabolism, glycolysis, pyruvate metabolism and SCFAs transport were facilitated and the methanogenesis was inhibited on the contrary with SP-lysozyme treatment, which was undoubtedly responsible for the superior SCFAs accumulation in anaerobic fermentation process. Considering the carbon resource recovery in SCFAs form, such novel SP-lysozyme treatment exhibited 325.1 CNY /ton SS (45.5 USD / ton SS) economic benefit and avoided 0.12 CO2/ton SS carbon emission, suggesting its promising application potential in future WAS management.