Background: Hydrofluoric acid (HF) is a small and partially dissociated acid (pKa 3.2), able to deeply penetrate into human skin in addition to the corrosiveness of the hydrogen ion (H+) and the toxicity of the fluoride ion (F−). However, there has been a lack of experimental studies to objectively characterize the results of human HF skin exposure decontamination.Methodology/principal findings: A previously established experimental method using a human skin explants ex vivo model (Part 1. Experimental 70% hydrofluoric acid (HF) burns: Histological observations in an established human skin explants ex vivo model) described the lesions that appeared following 70% HF penetration. Within 5 min, 70% HF penetrates to the dermis. Using the same experimental conditions, a comparison study of two different washing protocols was performed: water + topical calcium gluconate (CaG) versus Hexafluorine®. In these conditions, washing for 15 min with running tap water followed by topical CaG ointment only delayed burn onset, while severe tissue damage appeared later. In contrast, after washing with Hexafluorine® over 10 min, no histological lesions developed. These results are in accordance with the results of accidental human industrial case reports.Conclusion/significance: Amphoteric and hypertonic Hexafluorine® can deactivate H+ and chelate F− ions. Based on these results, it should be considered as a promising first-aid decontamination solution to prevent or minimize significant local and systemic consequences of concentrated HF skin exposures.