5-Hydroxymethylfurfural (HMF) is one of the most important lignocellulosic biomass-derived platform molecules for production of renewable fuel additives, liquid hydrocarbon fuels, and value-added chemicals. The present work developed niobium oxides (Nb2O5) supported on mesoporous carbon/silica nanocomposite (MCS), as novel solid base catalyst for synthesis of HMF via one-pot glucose conversion in a biphasic solvent. The MCS material was prepared via carbonization using natural rubber dispersed in hexagonal mesoporous silica (HMS) as a precursor. The Nb2O5 supported on MCS (Nb/MCS) catalyst with an niobium (Nb) loading amount of 10 wt.% (10-Nb/MCS) was characterized by high dispersion, and so tiny crystallites of Nb2O5, on the MCS surface, good textural properties, and the presence of Bronsted and Lewis acid sites with weak-to-medium strength. By varying the Nb loading amount, the crystallite size of Nb2O5 and molar ratio of Bronsted/Lewis acidity could be tuned. When compared to the pure silica HMS-supported Nb catalyst, the Nb/MCS material showed a superior glucose conversion and HMF yield. The highest HMF yield of 57.5% was achieved at 93.2% glucose conversion when using 10-Nb/MCS as catalyst (5 wt.% loading with respect to the mass of glucose) at 190 °C for 1 h. Furthermore, 10-Nb/MCS had excellent catalytic stability, being reused in the reaction for five consecutive cycles during which both the glucose conversion and HMF yield were insignificantly changed. Its superior performance was ascribed to the suitable ratio of Brønsted/Lewis acid sites, and the hydrophobic properties generated from the carbon moieties dispersed in the MCS nanocomposite.