The combination of hollow mesoporous structure and magnetic resonance (MR) contrast agent has shown its potential in simultaneous drug delivery and cell tracking applications. However, the preparation of this kind of nanocomposites is complicated and usually takes several days, which are unsuitable for scaled-up production. To conquer those hurdles, we report herein on a facile method to synthesize iron oxide hydroxide functionalized hollow mesoporous silica spheres (FeOOH/HMSS) in one-step manner. By carefully controlling the reaction kinetics of K2FeO4 in water, gram-scale production of FeOOH/HMSS can be readily prepared at 60°C for as short as 30 min. Most importantly, this synthetic process is also cost-effective and eco-friendly in both precursor (K2FeO4 and H2O) and product (FeOOH). The mechanism of the formation of hollow structure was carefully investigated, which should be due to the synergetic effect of surfactant CTAB and side product KOH. Having outstanding biocompatibility, these degradable nanocolloids also demonstrate its feasibility in in vitro/vivo MR imaging and in vitro drug delivery.