The production of 5-hydroxymethylfurfural (5-HMF) from cellulose catalyzed by a series of transition metal chlorides (i.e. FeCl3, RuCl3, VCl3, TiCl3, MoCl3 and CrCl3) was studied in biphasic system. RuClas the most efficient catalyst among these transition metal chlorides for 5-HMF production, and resulted in both the highest yield of 83.3% and selectivity of 87.5% in NaCl-aqueous/butanol biphasic system. XRD analysis and FTIR spectroscopy were applied to further characterize the RuCl3 catalyzed cellulose slurries to reveal the catalytic reaction mechanism. Results demonstrated that RuCl3 enhanced the decrystallization and cleavage of C-O-C bonds in cellulose, promoted the subsequent dehydration of glucose into 5-HMF, while suppressed the glucose retro-aldol reaction to byproduct lactic acid. In addition, with the assistance of NaCl-aqueous/butanol biphasic system, 5-HMF further degradation was limited and thusly maintained a desired 5-HMF yield. This proposed approach provides an efficient strategy for one-pot conversion of cellulose into 5-HMF.