A novel inorganic-organic hybrid nanocatalyst has been prepared by initially functionalizing titanate nanotubes with 3-amino-propyltrimethoxysilane and subsequently introducing sulfonic acid groups with 1,4-butane-sultone. The as-prepared hybrid catalyst was characterized by FT-IR, XRD, TEM, SEM-EDX, TG-DTG, and N2 adsorption isotherm techniques, and its catalytic performance was evaluated by esterification of levulinic acid with n-butyl alcohol under solvent-free conditions. The experimental design and study were carried out by response surface methodology (RSM) to test the effects of reaction conditions on the catalytic process. Up to 82.7% yield of n-butyl levulinate was obtained under the optimal reaction conditions. Furthermore, the catalyst showed an excellent reusability without the loss of reactivity after several runs.