To well address the problem of low stability for Ru-based catalysts against sintering and leaching during synthesis and aqueous levulinic acid (LA) hydrogenation to gamma-valerolactone (GVL), herein we demonstrate an "inside-to-outside" synthetic strategy for robust yolk-structured nanospheres within a single Ru nanoparticle (NP, 4.2 nm) anchored inside the mesoporous shell (pore size, 4.0 nm), denoted as YS Ru@HMCS (yolk-structured Ru encapsulated into hollow mesoporous carbon sphere). Such a shell-supported-core configuration combines the merits of conventional yolk-structured and supported types, in which the active core is not only fully exposed, but also strongly anchored on the shell, based on the optimized interaction between oxidized Ru NP and N-doped mesoporous carbon shell. As a consequence, the resultant YS Ru@HMCS, delivers a high LA conversion (99.4%), a large selectivity to GVL (99.9%), and prolonged cycling life (up to 9 cycles) under water towards the LA hydrogenation, that exceeds conventional yolk-structured and supported analogues. Sintering-resistant, a single Ru NP is successfully encapsulated, and its leaching-resistant property is enhanced based on the improved metal-support contact, thus affording a highly stable Ru catalyst. Moreover, such a synthetic concept can be extended to the stabilization of other supported catalysts, providing a general approach to enhancing both the thermal and chemical stability of supported nanocatalysts. (C) 2020 Elsevier Inc. All rights reserved.