A hybrid model combining hydrodynamic and biological effects is developed to describe the cultivation of Acetobacter xylinum for bacterial cellulose production in a modified airlift reactor with wire-mesh draft tubes. The hydrodynamic part is essentially a modified tanks-in-series model whose parameters are determined using a tracer response method. The modified tanks-in-series model is based on that the materials in the riser and downcomer are exchangeable across the wire-mesh draft tube. In addition, the effect of oxygen transfer is also taken into consideration for the tanks-in-series model. An artificial neural network (ANN) model based on the data of a batch cultivation in a stirred tank reactor combined with system equations is utilized as the biological part. Simulation is carried out to demonstrate that the proposed hybrid model represents the cultivation system very well.