AbstractWith the progression of the COVID-19 pandemic, large datasets of SARS-CoV-2 genome sequences were collected to closely monitor the evolution of the virus and identify the novel variants/strains. By analyzing genome sequencing data, health authorities can ‘hunt’ novel emerging variants of SARS-CoV-2 as early as possible, and then monitor their evolution and spread. We designed VariantHunter, a highly flexible and user-friendly tool for systematically monitoring the evolution of SARS-CoV-2 at global and regional levels. In VariantHunter, amino acid changes are analyzed over an interval of 4 weeks in an arbitrary geographical area (continent, country, or region); for every week in the interval, the prevalence is computed and changes are ranked based on their increase or decrease in prevalence. VariantHunter supports two main types of analysis: lineage-independent and lineage-specific. The former considers all the available data and aims to discover new viral variants. The latter evaluates specific lineages/viral variants to identify novel candidate designations (sub-lineages and sub-variants). Both analyses use simple statistics and visual representations (diffusion charts and heatmaps) to track viral evolution. A dataset explorer allows users to visualize available data and refine their selection. VariantHunter is a web application free to all users. The two types of supported analysis (lineage-independent and lineage-specific) allow user-friendly monitoring of the viral evolution, empowering genomic surveillance without requiring any computational background.Database URLhttp://gmql.eu/variant_hunter/