Expectations for energy storage are high but large-scale underground hydrogen storage in porous media (UHSP) remains largely untested. This article identifies and discusses the scientific challenges of hydrogen storage in porous media for safe and efficient large-scale energy storage to enable a global hydrogen economy. To facilitate hydrogen supply on the scales required for a zero-carbon future, it must be stored in porous geological formations, such as saline aquifers and depleted hydrocarbon reservoirs. Large-scale UHSP offers the much-needed capacity to balance inter-seasonal discrepancies between demand and supply, decouple energy generation from demand and decarbonise heating and transport, supporting decarbonisation of the entire energy system. Despite the vast opportunity provided by UHSP, the maturity is considered low and as such UHSP is associated with several uncertainties and challenges. Here, the safety and economic impacts triggered by poorly understood key processes are identified, such as the formation of corrosive hydrogen sulfide gas, hydrogen loss due to the activity of microbes or permeability changes due to geochemical interactions impacting on the predictability of hydrogen flow through porous media. The wide range of scientific challenges facing UHSP are outlined to improve procedures and workflows for the hydrogen storage cycle, from site selection to storage site operation. Multidisciplinary research, including reservoir engineering, chemistry, geology and microbiology, more complex than required for CH4 or CO2 storage is required in order to implement the safe, efficient and much needed large-scale commercial deployment of UHSP.