Improving sulfur redox kinetics and cycling stability of lithium-sulfur (Li-S) batteries through controlling inherent dissolution of polysulfides and following shuttle effect is pivotal for further progress of this promising electrochemical system. In this work, three-dimensional porous microspheres composed of nanosized sulfur particles, nitrogen-doped oxygen-deficient TiO2-x nanorods and reduced graphene oxide (N-TiO2-x/RGO/S) were synthesized as sulfur host material for the first time in spray-drying process. The microspheres construction with void spaces mitigated volumetric expansion upon charge/discharge cycling and improved sulfur utilization. Furthermore, the N-TiO2-x nanorods enhanced the conductivity of the material and exhibited strong capability for adsorption and the migration of lithium polysulfides, which was demonstrated by the density functional theory (DFT) calculations. Due to such advantages, the N-TiO2-x/RGO/S cathode delivered excellent rate capability and stable cycle performance at 1.0 C over 300 cycles with a specific capacity about 700 mAh g-1. This novel design and preparation strategy also contributes to the materials engineering and structural design towards remarkable improvement of electrochemical performance of energy storage systems.