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Abstract: With the increasing heavy and inferior quality of global oil resources, the efficient utilization of crude oil has become a critical challenge to be solved in the energy field. This work intends to propose a feasible way of crude oil pretreatment in the refining process. A comparison of the comprehensive performance differences between thermal processing (TP) and slurry phase hydroupgrading (SPH) treatments revealed that SPH had a great upgrading effect for Arabian heavy crude oil under 390 °C and oil-soluble MoS2 catalyst. Compared with the feedstock, the asphaltene content of TP product increased by 13.2 wt%, that in SPH product dropped by about 19.8 wt%. And the total distillate yield (≤540 °C) of SPH increased by 4.4 wt% compared to the TP. The results of SARA separation and X-Ray Diffraction (XRD) showed that SPH can not only inhibit the occurrence of free radical reactions, but also dissociate the original asphaltene. The detailed composition of the processed samples was characterized by gas chromatography-mass spectrometry (GC-MS) and electrospray ionization orbitrap mass spectrometry (ESI Orbitrap MS) to explore the molecular transformation mechanism of different processes. There are a considerable number of –S– bonds in asphaltene as important structural connection hubs. The process of SPH can promote the production of light hydrocarbons while effectively removing heteroatom compounds. Finally, we considered that it is necessary to carry out the SPH pretreatment for Arabian heavy crude oil.