Polynitroadamantanes are the precursors both in pharmaceutical synthesis and energetic material preparation. In this paper, the determination method of 2, 2-nitroadamantane and 2, 2, 4, 4, 8, 8-hexanitroadamantane was established by High Performance Liquid Chromatography (HPLC) with optimal chromatographic conditions including the detector, mobile phase and stationary phase. The Ultraviolet detector and DIONEX C18 column (5 μm, 120 A, 4.6 mm×250 mm) were confirmed to get base line separation and high limit of detection for these two compounds mixture. The acetonitrile/water (80/20, V/V) was employed as mobile phases, which presented exceptional separation effect on these two targets when the flow rate was 1.0 mL·min^-1. Results show that the detection limit, linear range, the linear correlation coefficient and precision of 2, 2-nitroadamantane are 0.003 mg·mL^-1, 0.005-1.000 mg·mL^-1, 0.9987 and 1.382%, respectively. Correspondingly, the same parameters of 2, 2, 4, 4, 8, 8 -hexanitroadamantane are 0.001 mg·mL^-1, 0.005-1.000 mg·mL^-1, 0.9984 and 1.300%, respectively