The world’s first high-temperature gas-cooled reactor pebble-bed module (HTR-PM) nuclear power plant adopts an innovative reactor type and a modular structure design. Parameter estimation and model calibration are of great significance prior to the implementation of model-based control and optimization. This paper focuses on identifying the thermal hydraulic parameters of HTR-PM over the global operating domain. The process technology and model mechanism of HTR-PM are reviewed. A parameter submodel named global parameter mapping is presented to quantify the relationship between an unknown model parameter and different operating conditions in a data-driven manner. The ideal construction of such a mapping requires reliable estimates, a well-poised sample set and an appropriate global surrogate. An adaptive model calibration scheme is designed to tackle these three issues correspondingly. First, a systematic parameter estimation approach is developed to ensure reliable estimates via heuristic subset selection consisting of estimability analysis and reliability evaluation. To capture the parameter behavior among the multiple experimental conditions and meanwhile reduce the operating cost, an adaptive experimental design is employed to guide condition testing. Experimental conditions are sequentially determined by comprehensively considering the criteria of sampling density, local nonlinearity and parameter uncertainty. Support vector regression is introduced as the global surrogate due to its capability of small-sample learning. Finally, the effectiveness of the model calibration scheme and its application performance in HTR-PM are validated by the simulation results.