The analysis of fluroescence tagged proteins in live cells from multi-channel microscopy image sequences requires a registration to a reference frame to decouple the movement and deformation of cells from the movement of proteins. We have developed an intensity-based approach for the registration of 2D and 3D multi-channel microscopy image sequences. This approach can be directly applied to the intensity images or to the segmented images. Also, we have performed a comparison using a direct registration scheme to the reference frame and an incremental scheme taking into account results from preceding time steps. We have evaluated our approach based on 3D synthetic images of a simulated spherical cell with known deformation which has been calculated based on an analytic solution of the Navier equation given certain boundary conditions. We have also successfully applied our approach to 2D and 3D real microscopy image sequences.