Iron minerals are important soil components; however, little information is available for the transformation of antibiotics on iron mineral surfaces, especially under limited moisture conditions. In this study, we investigated the catalytic performance of four iron minerals (maghemite, hematite, goethite, and siderite) for the hydrolysis of chloramphenicol (CAP) antibiotic at different moisture conditions. All the iron oxides could efficiently catalyze CAP hydrolysis with the half-lives <6 days when the surface water content was limited, which was controlled by the atmospheric relative humidity of 33-76%. Different minerals exhibited distinctive catalytic processes, depending on the surface properties. H-bonding or Lewis acid catalysis was proposed for surface hydrolytic reaction on iron oxides, which however was almost completely inhibited when the surface water content was >10 wt % due to the competition of water molecules for surface reactive sites. For siderite, the CAP hydrolysis was resistant to excessive surface water. A bidentate H-bonding interaction mechanism would account for CAP hydrolysis on siderite. The results of this study highlight the importance of surface moisture on the catalytic performance of iron minerals. The current study also reveals a potential degradation pathway for antibiotics in natural soil, which has been neglected before.