Aiming at the multi-constraint terminal guidance of hypersonic vehicle, a novel 3D (three-dimensional) nonlinear adaptive terminal guidance law was proposed to resolve the problems of channel coupling, parameter perturbation and model mismatching. For the integrality and concision in model description, a 3D guidance reference model and its corresponding practical guidance system were both constructed on the basis of the concepts about line-of-sight twist and its rate. In order to guarantee the robustness and adaption, a 3D nonlinear adaptive guidance law was deduced on the basis of the adaptive control theory. The stability of this guidance law was proved through mathematical deduction. With this novel guidance law, the channel coupling, parameter perturbation and model mismatching problems were avoided and the multiconstraint of terminal guidance was satisfied as well. The validity of this guidance law was also validated through simulation experiments.