Updated publication reference for PubMed record(s): 28634367. A recent algicidal mode indicates that fungal mycelia can wrap and eliminate almost all the co-cultivated algal cells within a short time. However, the regulation of molecular mechanism is rarely understood. Here, proteomic analysis was applied to investigate the algicidal process of Trametes versicolor F21a. Our results showed that 3,754 fungal proteins were identified, among which 2,809 unique proteins could be quantified during the process. 30 isoenzymes with the capacity of degradation biomass, belonging to Glycoside Hydrolases, Auxiliary Activities, Carbohydrate Esterases and Polysaccharide Lyases, were significantly up-regulated, suggesting that these enzymes probably employed synergistic mechanisms in degrading algal cells. Additionally, peptidase, exonuclease, manganese peroxidase and cytochrome c peroxidase were also up-regulated. 10% of the significantly up-regulated proteins were extracellular enzymes. Gene Ontology (GO) and KEGG pathway enrichment analysis demonstrated that the enriched metabolic pathways mainly contained carbon metabolism, selenocompound metabolism, sulfur assimilation and metabolism, as well as several amino acid biosynthesis pathways, which implied that these pathways should play vital roles in the synthesis of needed nutrition for the fungal mycelia via components of algal cells. Moreover, the fungal NmrA-like transcriptional regulator which represses the nitrogen metabolite was also enriched and might be a key regulator in eliminating algal cells