This paper presents a novel self-calibration strategy for a general hexapod manipulator to overcome weaknesses and embrace merits of existing approaches. A commercial trigger probe and a cylindrical gauge block are adopted in the present approach. The algorithm is formulated to solve a nonlinear least squares problem that takes all measurement errors into account. The simulation results show that the proposed algorithm has the following advantages: (1) it is capable of calibrating the position and orientation of the gripper or spindle on the platform; (2) it completely avoids the unobservability of certain parameters due to mobility constraints on the passive joints; (3) the hardware of the calibration system is more compact and cost-effective than that adopted in the existing approaches; and (4) the algorithm is numerically robust, efficient and effective, while the calibrated parameter errors are expected to be with the same order of the measurement errors. Due to these merits, the present scheme is attractive for an autonomous hexapod manipulator when a great precision is required in a workspace of five degrees-of-freedom.