Elucidating the underlying structure-performance relationship of Fe3O4-containing catalysts for the aquathermolysis of crude oil is essential for the design of efficient heterogeneous catalysts. Therefore, recyclable Fe3O4 nanoparticles (NPs) with different morphology and particle size were first prepared and tested for catalytic aquathermolysis. The easily prepared Fe3O4 NPs with irregular morphology (L-Fe3O4) have larger inter crystalline mesopores than oleic acid-modified Fe3O4 NPs. This leads to enhanced mass transfer ability, more accessible active sites and thus better aquathermolysis performance. Moreover, these L-Fe3O4 NPs were loaded on a heulandite support by a scalable co-precipitation method, and this L-Fe3O4/heulandite catalyst showed very good performance in catalytic aquathermolysis, with a viscosity decrease of extra-heavy crude oil of 85.0%. The underlying structure-performance relationship was systematically investigated by XRD, HRTEM, EDX-mapping, FT-IR, elemental analysis, SARA (saturate, aromatic, resin and asphaltene) analysis and H-1 NMR. The Fe3O4/heulandite catalyst broke C-S bonds and reduced the resin and asphaltene content of the oil. This work is important for the design of Fe3O4-containing catalysts in catalytic aquathermolysis.