An observer-based adaptive controller developed from a hierarchical fuzzy-neural network (HFNN) is employed to solve the controller time-delay problem for a class of multi-input multi-output (MIMO) non-affine nonlinear systems under the constraint that only system outputs are available for measurement. By using the implicit function theorem and Taylor series expansion, the observer-based control law and the weight update law of the HFNN adaptive controller are derived. According to the design of the HFNN hierarchical fuzzy-neural network, the observer-based adaptive controller can alleviate the online computation burden. Moreover, the common adaptive controller is utilized to control all the MIMO subsystems. Hence, the number of adjusted parameters of the HFNN can be further reduced. In this paper, we prove that the proposed observer-based adaptive controller can guarantee that all signals involved are bounded and that the outputs of the closed-loop system track asymptotically the desired output trajectories.