Virtual boundary meshfree Galerkin method (VBMGM) is developed to solve the multi-domain variable coefficient heat conduction problem with heat source. Both the virtual source function on the virtual boundary and heat source within each subdomain are approximate by the radial basis function interpolation. The equation of the proposed technique is derived by one of the weighted residual methods, namely the Galerkin method, for multi-domain variable coefficient heat conduction problem with heat source. Therefore, VBMGM simultaneously possesses the merits of Galerkin method, boundary element method and meshfree method. And the numerical meanings of the weighted values are definite, such as the partial derivative heat source expressions, the temperature, the heat flux and the continuity conditions, in VBMGM for multi-domain variable coefficient heat conduction problem with heat source. The specific and detailed equation of VBMGM is obtained for multi-domain variable coefficient heat conduction problem with heat source. The accuracy and the stability of the proposed technique are validated by two numerical examples for multi-domain variable coefficient heat conduction problem with heat source. (C) 2016 Elsevier Ltd. All rights reserved.