Methyl isobutyl ketone (MIBK) as a solvent is extensively used for the phenols extraction from the wastewater, so it is unavoidable to expose in the effluent due to the solubility and leakage problem. The present study evaluated the impact of MIBK on phenols degradation in an UASB reactor and analyzed its degradation properties. The results indicated that the continuous dosing (0.1 g L⁻¹) and impact (10 g L⁻¹) of MIBK had limited effect on phenols removal (1–2% reduction) in the UASB reactor, but the specific methanogenic activity (SMA) values of sludge decreased by 45–75% after MIBK exposure. Anaerobic degradation rate of MIBK fitted well to a pseudo-first-order kinetic equation with respect to the initial concentration of 35 mg L⁻¹ (k = 0.0115 h⁻¹, R² = 0.9664). Furthermore, the relative methane generation rate constants of MIBK were 0.00816, 0.00613, 0.00273, and 0.00207 d⁻¹ at the initial concentrations of 0.1, 0.5, 5, and 10 g L⁻¹, respectively. MIBK showed higher inhibitory effect on the methanogenesis than on phenols degradation. This study pointed out that the industrial installations should consider the influence of solvent on anaerobic treatment of phenolic wastewater.