Despite being one of Earth’s most abundant polymeric organic compounds, lignin is often considered a lower-value byproduct in industrial processes. Converting lignin into valuable chemicals or biomaterials requires a thorough structural characterisation of depolymerised products. This non-targeted analysis method involving 2D liquid chromatography and high-resolution tandem mass spectrometry uses SIRIUS in versatile ways to unravel the complex structures of depolymerized lignin.