The influence of structure on degradation of five halogenated phenols (XPs) by UV/H2O2 process was investigated. The combined influence of type or number of substituents and UV/H2O2 process parameters (pH and [H2O2]) on the degradation kinetics of 2-fluorophenol (2-FP), 2-chlorophenol (2-CP), 2-bromophenol (2-BP), 2,4-dichlorophenol (2,4-DCP), and 2,4,6-trichlorophenol (2,4,6-TCP) was studied using modified miscellaneous 33 full factorial design and response surface modeling (RSM). Studied XPs obey first-order degradation kinetics within the investigated range of process parameters. Determined degradation rate constants (k obs) were correlated with process and structural parameters by the quadratic polynomial models. Analysis of variance (ANOVA) demonstrated RSM models’ accuracy and showed that, in addition to pH and [H2O2], model terms related with the pollutant structure are highly influential. k obs of mono-XPs follow the decreasing order 2-FP, 2-CP, and 2-BP, while CPs follow the decreasing order 2-CP, 2,4-DCP, and 2,4,6-TCP. Biodegradability (biochemical oxygen demand (BOD)5/chemical oxygen demand (COD)) and toxicity (TU) were evaluated prior to the treatment and at the reference time intervals. The observed differences are correlated with the structural characteristics of studied XPs.