The coupled heat, air and moisture transfer between building envelopes and indoor air is complicated, and has a significant influence on the indoor environment and the energy performance of buildings. However, in most building energy analysis the calculation of heat conduction through walls usually neglects the transport and storage of moisture in porous building materials and the interaction between hygrothermal transfer and multi-zone airflow inside the building. In the paper, a model for predicting coupled multi-zone hygrothermal-airflow transfer is presented. Both heat and moisture transfer in the building envelope and multi-zone indoor airflow are simultaneously considered; their interactions are modelled. The coupled system model is validated by using a series of testing tools and experiments. The new program is applied to investigate the moisture transfer effect on indoor air humidity and building energy consumption in different climates (hot-humid, temperate and hot-dry climates). The results show that not accounting for hygrothermal effects in modelling will result in overestimation of energy costs for hot and humid climate situations and possible over sizing of plant leading to inefficient operation.