Abstract: Gallium, indium, germanium, selenium and tellurium are extremely scarce and widely dispersed in the Earth’s crust, which have been included in the critical mineral list due to their extensive application in modern clean energy transitions. Traditional analytical methods are limited by their weak mass spectrometric response and severe interference (especially selenium), requiring the use of two techniques, inductively coupled plasma-mass spectrometry (ICP-MS) and hydride generation atomic fluorescence spectrometry (HG-AFS), which cannot achieve simultaneous determination of the same sample after one dissolution. An open-vessel digestion with HF-HNO₃-HClO₄ was employed to prevent volatilization of Ge and Se while ensuring complete decomposition. Isopropanol (2%, V/V) was selected as a sensitizer to improve the MS response of ⁸⁰Se and ¹²⁸Te by 2.75- and 2.32-fold, respectively. The severe mass spectrometric interference on ⁸⁰Se was eliminated by the mass-shift mode with oxygen as the reaction gas in inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS), and the signal-to-noise ratio for Se reached 58.20. A simultaneous determination method for Ga, In, Ge, Se and Te by ICP-MS/MS was established in this study. The detection limits of this method ranged from 0.002 to 0.060g/g, and the ΔlgC values for six certified reference materials were all within ±0.05, with an RSD of <5%. The method established in this study addresses the drawbacks of Ge and Se being prone to volatilization loss during digestion, the poor MS response of Se and Te, and the severe interference on Se in single-quadrupole ICP-MS, which typically necessitates aqua regia semi-digestion. This method achieves the simultaneous determination of the five critical mineral elements Ga, In, Ge, Te, and Se in typical geological samples (soil and stream sediments) in a single run.