The Permian Period is punctuated by Earth system changes unlike any other in geological history. The start of the Permian witnessed the termination of the Late Paleozoic Ice Age, followed by the climatic transition from icehouse to greenhouse conditions. The Guadalupian-Lopingian (Middle-Late Permian) was characterized by two biocrises associated to volcanisms: (i) the end-Guadalupian crisis and (ii) the end-Permian mass extinction. Seawater Sr isotope (87Sr/86Sr) records can shed light on the evolution of the Permian Earth system. The Permian 87Sr/86Sr record suffers from a number of issues including low resolution and potential diagenetic alteration. In this paper, we summarize the existing Permian 87Sr/86Sr records and focus on the current challenges. We also present a new, high-resolution Permian 87Sr/86Sr curve derived from pristine brachiopod shells based on data resulting from careful diagenetic screening. Our new record shows that the 87Sr/86Sr of seawater decreased continuously from the earliest Permian to the middle Capitanian (late Guadalupian), with the lowest ratio of 0.706832 registered in the Colania douvillei-Kahlerina pachiytheca Zone. Subsequently, 87Sr/86Sr ratios increased from the late Capitanian to the latest Permian and reached a ratio of 0.707167 just 0.8 m below the first occurrence of the Hindeodus parvus. We employed a stochastic oceanic box model to explore the potential drivers of the Permian seawater Sr isotope record. Our results support that changes in the hydrothermal input, rather than changes in continental weathering intensity, are the most likely controlling factor for the observed variations in Permian seawater 87Sr/86Sr. Therefore, we suggest that the marine hydrothermal system (and hence ocean basin dynamics and deep-sea temperatures) may have been the driver of the pronounced decreasing 87Sr/86Sr trend across the Permian.