Abstract Understanding formation of organo-mineral association is crucial for soil organic matter (SOM) stabilization. To remove reactive minerals from un-disturbed natural soil (NS) and two cultivated soils (dry-farming soil, TD, and terrace paddy soil, TP), a 10% HF/1M HCl treatment was applied. The mineral protection of different molecular SOM structures before and after cultivation was compared by using markers for lipid and lignin. The removal of reactive mineral increased the lipid extractability in TD and NS similarly, indicating that the cultivation did not reduce the mineral protection; this is attributable to fertilizer application and amorphous Fe oxide enrichment. In TP, the extent of lipid protection was lower than in TD, demonstrating that the protection depends on the type of cultivation. In contrast to lipids, lignin-derived phenols decreased over 80% after acid treatment. Furthermore, the ratios of acid to aldehyde in vanillyl ((Ad/Al) V) of TD and TP were much higher than in NS, indicating an increased oxidation of lignin in cultivated soils. During acid treatment, two distinct layers of soil particles were identified: an organic matter (OM)-enriched layer (L OM), and a non-reactive mineral-enriched layer (L NR) with hardly detectable OC content. However, up to 50% of lipids were detected in L NR , indicating that lipids did not selectively interact with reactive mineral particles. In TD and TP, (Ad/Al) V values were higher in L OM than in L NR , indicating a strong interaction of oxidized lignin in L OM. Therefore, the protection of lignin, especially highly oxidized lignin, can depend more on reactive minerals than lipid. Promoting the formation of organo-mineral complexes is the primary strategy for soil management, especially for highly oxidized OM. Graphical abstract Image 1 Highlights • Lipids protected by minerals did not decrease after cultivation. • Lipid protection by minerals was lower in dry-farming than in paddy soils. • Lipid protection depends less on reactive minerals than lignin does. • Removal of reactive minerals sharply decreased lignin-derived phenol contents. • Highly oxidized lignin was strongly protected by reactive minerals. [ABSTRACT FROM AUTHOR]