UV/H2O2 and UV/peroxodisulfate (PDS) processes were adopted to degrade a typical beta-blocker atenolol (ATL). The degradation efficiencies under various operational parameters (oxidant dosage, pH, HCO3-, humic acid (HA), NO3-, and Cl-) were compared. Principal factor analysis was also performed with a statistical method for the two processes. It was found that increasing the specific dosage of the two peroxides ([peroxide]0/[ATL]0) ranging from 1:1 to 8:1 led to a faster degradation rate but also higher peroxide residual. Within the pH range 3-11, the optimum pH was 7 for the UV/PDS process and elevating pH benefitted the UV/H2O2 process. The presence of HCO3-, HA, and Cl- adversely affected ATL oxidation in both processes. The NO3- concentration 1-3 mmol/L accelerated the destruction of ATL by the UV/PDS process, but further increase of NO3- concentration retarded the degradation process, contrary to the case in the UV/H2O2 process. The rank orders of effects caused by the six operational parameters were pH approximately specific dosage > [HA]0 > [NO3-]0 > [HCO3-]0 > [Cl-]0 for the UV/H2O2 process and specific dosage > pH > [HA]0 > [NO3-]0 > [HCO3-]0 > [Cl-]0 for the UV/PDS process. The UV/PDS process was more sensitive to changes in operational parameters than the UV/H2O2 process but more efficient in ATL removal under the same conditions.