Deep removal of organic sulfur from fuel has become an important issue worldwide in the field of energy and environment. In this work, a novel approach for efficient adsorption-desulfurization in which both the adsorption and separation processes were performed simultaneously was demonstrated in a two stage hydrocyclones pilot trial. We applied mass-produced MOF-199 as the adsorbent and dibenzothiophene (DBT) dissolved in dodecane as the model fuel. The adsorption dynamics and the significant influences of the dosage of adsorbent, the inlet flow rate and the split ratio on the removal efficiency were investigated to match the simultaneous adsorption-separation processes. After optimizing the operating conditions, the ultimate DBT concentration in the outlet of the two-stage hydrocyclones was 8.79 ppmw, which was less than the regulatory target of 10 ppmw; the separation efficiency of MOF-199 particles was as high as 99.75% within 30 s at an initial DBT concentration of 50 ppmw and a dosage of MOF-199 of 5 wt.%. More importantly, MOF-199 can be successfully regenerated using H2O2 oxidation at the laboratory scale. The exceptionally high removal efficiency, fast separation speed, low cost and simple equipment make this simultaneous adsorption-separation hydrocyclone process a promising deep-desulfurization method. (C) 2017 Elsevier B.V. All rights reserved.