As an important biomass-derived chemical, o-sorbitol can be converted to a variety of useful chemicals and fuels. Because of the strong nucleophilicity of I- and reducibility of hydrogen iodide (HI), hydroiodic acid has been used for polyol hydrogenolysis with high selectivity. Here, D-sorbitol was converted by HI, rhodium, and hydrogen to give a high yield of iodohexanes (94.2%) at 373 K in a water/cyclohexane biphasic system. Rhodium and hydrogen were used to regenerate HI in situ. The reaction mechanism was studied in detail by using model molecules. The substitution-elimination-addition (SEA) mechanism was proven to be the most possible pathway. The high concentration of both proton and iodide was found to be necessary for the efficient conversion of D-sorbitol and the selective formation of iodohexanes. Besides, water could inhibit the conversion of D-sorbitol dramatically. These findings were explained by kinetic study and demonstrated in the reaction kinetic equation. This catalytic system, including HI and RhCI3, was proven to be reusable. In addition, iodohexanes can be quantitatively converted to hexenes over ZrO2 at 473 K.