This two-volume set constitutes the proceedings of the 22nd International Conference on Web Information Systems Engineering, WISE 2021, held in Melbourne, VIC, Australia, in October 2021.The 55 full, 29 short and 5 demo papers, plus 2 tutorials were carefully reviewed and selected from 229 submissions. The papers are organized in the following topical sections:Part I: BlockChain and Crowdsourcing; Database System and Workflow; Data Mining and Applications; Knowledge Graph and Entity Linking; Graph Neural Network; Graph Query; Social Network; Spatial and Temporal Data Analysis.Part II: Deep Learning (1), Deep Learning (2), Recommender Systems (1), Recommender Systems (2), Text Mining (1), Text Mining (2), Service Computing and Cloud Computing (1), Service Computing and Cloud Computing (2), Tutorial and Demo.