Energy pile is an established approach to allow harvesting geothermal energy while fulfilling its role in supporting structural loads. The environmental responsiveness also means new operational factors beyond the conventional structural loads need to be considered, i.e., the change of soil-pile interactions resulting from thermal expansion/contraction cycles as well as non-isothermal conditions associated with the geothermal heat exchangers (GHEs). These are the resultants of the coupled thermo-hydro-mechanical processes driven by the cyclic thermal boundary conditions. To holistically simulate the thermo-hydro-mechanical interactions of energy pile, this study implements a 3D computational model, for which the non-isothermal GHE pipe flow and soil-pile interaction are taken into account. The soil-pile interactions are described by interface model that describes the variations in the characteristics of soil-pile interface resistance and end bearing. The influence of non-isothermal conditions on the thermomechanical behavior of the energy pile is first analyzed. Then the model predicts the variations of soil-pile interactions including side friction and end bearing as well as the thermomechanical behavior of the pile. Besides, sensitivity analyses are conducted on the effects of thermodynamic and hydraulic factors on the soil-pile interaction of the energy pile in addition to energy production. Major findings include: (1) Strong end-restraint and soil shaft resistance make the thermal effects on the mechanical behaviors of energy pile to be more pronounced, which should be carefully considered in the practice; (2) Higher thermal conductivity of pile material and groundwater flow velocity benefit the thermal energy harvesting, but have insignificant effects on the mechanical behavior of energy pile; (3) The larger temperature difference between inlet and ground has negative effects on the axial load and shaft resistance at the soil-pile interface, however it benefits more energy extraction. The developed model will provide an important tool to analyze the behavior of energy pile and help improve the assumptions commonly used in the current design. (C) 2020 Elsevier Ltd. All rights reserved.