The invention discloses a coupling and drying process for preparing a cobalamine crystal, which adopts acetone or ethanol as a solventing-out agent and performs drying treatment in a dryer with stirring. The process comprises the following steps: 1) performing vacuum pumping treatment on a cobalamine wet crystal at the temperature in the dryer of 30 to 40 DEG C; 2) adjusting the temperature in the dryer to 40 to 50 DEG C, and introducing nitrogen or air into the dryer at intervals; 3) maintaining the vacuum pumping treatment state, adjusting the temperature in the dryer to 50 to 60 DEG C, preheating the temperature of an air source to 50 to 60 DEG C, and continuously introducing the air source into the dryer; and 4) maintaining the temperature in the dryer to 50 to 70 DEG C, and continuously performing vacuum pumping treatment. The process has the advantages that: by adding gas, the process enhances the mass transfer function and shortens the drying time. The detection shows that by adopting the process to dry the cobalamine crystal, the processing time is only 5 to 9 hours, the content of residual solvent in the crystal is less than or equal to 0.5 percent, the moisture content is less than or equal to 2 percent, the drying effect is good and the operation is simple.