As an excellent hydrogen storage medium, methanol has many advantages, such as high hydrogen content (12.6 wt%), low-cost and availability from biomass or photocatalysis. However, conventional methanol-water reforming usually proceeds at high temperature. In this research, we successfully designed a new effective strategy to generate hydrogen from methanol at near-room temperature. The strategy involves two main procedures, which are CH3OH→HCOOH→H2 and NADH→HCOOH→H2. The first procedure (CH3OH→HCOOH→H2) is performed by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and the Ir-catalyst. The second procedure (NADH→HCOOH→H2) is performed by formate dehydrogenase (FDH) and the Ir-catalyst. The Ir-catalyst is a reported polymer complex catalyst Cp*IrCl2(ppy), which owns high catalytic activity for formic acid decomposition at room temperature and compatibility to the enzymes, coenzyme and poisonous chemicals. This research reveals that the optimum hydrogen generation rate can reach up to 17.8 μmol h-1 g-1 under weak basic condition at 30 ℃. It will have high impact on hydrogen storage, production and applications, also provide a new inspiration for hydrogen generation from methanol.