In this paper, the work function Φ of the NdB6 (100) crystal surface have been determined by both theory and experiment. By the first-principles calculation, the Φ of NdB6 (100), (110), (111) and (210) crystal surfaces obey the relation of Φ(100) < Φ(210) < Φ(110) < Φ(111), and the theoretical value of Φ for (100) crystal surface is calculated to be 2.791 eV. The UPS measurement and the experiments of thermionic emission have been performed on the high-quality [100] NdB6 single crystal, which is prepared by the method of two optical floating zone melting passes. The Φ of the NdB6 (100) crystal surface has been calculated to be 2.806 eV by the UPS measurement, while the average Φeff of the NdB6 (100) crystal surface is calculated to be 2.813 ± 0.109 eV. The good agreement between theoretical and experimental results indicates that the Φ of the NdB6 (100) crystal surface can be determined to be around 2.80 eV. Furthermore, the narrow Φ distribution range and the low FWHM extracted from the Miram curves and PWFD plots suggest the good emission uniformity of the NdB6 (100) crystal surface.