Diclofenac sodium (DCF) is a non-steroidal anti-inflammatory drug. It has been classified as ecotoxic even at low concentrations. In this study, adsorption of DCF on coconut shell-based granular activated carbon (GAC) and regeneration of spent GAC with hydrochloric acid (HCl) were investigated. The results showed that GAC with heterogeneous surface structure adsorbs DCF endothermically with both chemical and physical forces. Adsorption and regeneration processes were optimized with Taguchi Experimental Design. The effects of all parameters affecting the adsorption and regeneration processes were determined by analysis of variance and Pareto analyses. DCF removal of 79.80% was obtained at optimum conditions and the most effective parameter was evaluated as GAC size. At optimum regeneration conditions, 6.85 mg DCF/g GAC adsorption capacity was found with an operating cost of euro0.05 g GAC. The amount of HCl was the most effective parameter. It was determined that the regenerated GAC had an adsorptive capacity higher than the adsorptive capacity of the raw GAC during at least three regeneration cycles. Raw, spent and regenerated GACs were characterized by Fourier transform infrared spectrometry and scanning electron microscopy analysis.