Metal-organic frameworks (MOFs) have been extensively studied on adsorptive desulfurization for their unique physical properties. However, the numbers of MOFs are increasing, and experimental research on screening ideal candidates for desulfurization is relatively not feasible. The high-throughput screening method was used to evaluate the top-performing MOFs for deep desulfurization. The uptake and selectivity of thiophene were computed based on the selected 716 MOF candidates in model fuels with the typical concentration of 224.6 ppmw (calculated by weight) at 293.15 K. The difference between GCMC and Henry selectivity indicated that the criteria of adsorption performance under the real conditions could not be simply evaluated with Henry selectivity. Based on the results, we chose two representatives to calculate pure thiophene and n-octane, as well as their mixture isotherms. These results highlight the importance of the structure-property relationship of potential MOFs for adsorptive desulfurization.