Abstract: The efficient separation of chalcopyrite (CuFeS₂) and galena (PbS) is essential for optimal resource utilization. However, finding a selective depressant that is environmentally friendly and cost effective remains a challenge. Through various techniques, such as microflotation tests, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) observation, X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy measurements, this study explored the use of ferric ions (Fe³⁺) as a selective depressant for galena. The results of flotation tests revealed the impressive selective inhibition capabilities of Fe³⁺ when used alone. Surface analysis showed that Fe³⁺ significantly reduced the adsorption of isopropyl ethyl thionocarbamate (IPETC) on the galena surface while having a minimal impact on chalcopyrite. Further analysis using SEM, XPS, and Raman spectra revealed that Fe³⁺ can oxidize lead sulfide to form compact lead sulfate nanoparticles on the galena surface, effectively depressing IPETC adsorption and increasing surface hydrophilicity. These findings provide a promising solution for the efficient and environmentally responsible separation of chalcopyrite and galena.