An alternative strategy for blocking the shuttling of soluble polysulfides in lithium-sulfur (Li-S) batteries involved introducing an interlayer between the cathode and separator. However, tailoring the interlayer components, structure, and chemistry to realize efficient conversion of polysulfides into insoluble lithium sulfides remains challenging. Herein, a flexible self-standing hybrid interlayer is engineered by intertwining one-dimensional (1D) V2O5 nanowires (NWs) with graphene nanoscrolls (GNS) into a robust interconnected 3D network to be used as both an upper current collector and physical/chemical polysulfide-trapper. The highly conductive and open GNS framework provides bicontinuous transfer channels for rapid electron and ion transport across the cathode/separator interface. Meanwhile, the V2O5 NWs act as ideal redox mediators to dynamically block polysulfide dissolution and facilitate their conversion into sulfides via formation of active intermediate polythionate complexes. Therefore, these cells with 70 wt% sulfur content in the whole cathode have significantly improved performance with a long cycling life (1000 cycles), low capacity decay (0.041% per cycle), and considerable areal capacity (>4 mA h cm-2), even at a high sulfur loading of 5.5 mg cm-2. This novel interlayer design strategy has great potential for promoting the practical use of Li-S batteries.