This study provides experimental results from batch and column studies to investigate diclofenac degradation by pyrite-Fenton process under variable chemical conditions (e.g., pyrite loading). Batch experiments show that diclofenac removal increased with increasing hydrogen peroxide and pyrite concentration. On the other hand, the addition of organic chelating agents such as citrate had an adverse effect on diclofenac removal by pyrite-Fenton process in batch systems due to scavenging effect of these agents for hydroxyl radicals. Batch results showed a direct correlation between the rate of diclofenac degradation and the rate of iron dissolution from pyrite, suggesting that diclofenac removal by pyrite-Fenton process was mainly controlled by solution phase hydroxyl radical attack on aromatic structure. Column experiments show that the effluent diclofenac concentration initially reached a peak value, and then sharply decreased to zero at higher pore volumes. The initial diclofenac breakthrough coincided well with the highest Fe(II) concentration observed in the breakthrough curve, implying that the generation of excess Fe(II) had a detrimental effect on removal efficiency due to scavenging effect of excess Fe(II) for hydroxyl radicals. The column system continued to function with 100% diclofenac removal efficiency when the effluent Fe(II) concentration decreased to a level at which the scavenging effect was minimized.