OBJECTIVE： To establish a method for simultaneous determination of lamotrigine （LTG）， Phenobarbital （PBB）， oxcarbazepine （OXC） and its active metabolite monohydroxycarbazepine （MHD） in human serum. METHODS： Serum samples were extracted with dichloromethane by liquid-liquid extraction， and then determined by RP-HPLC. Kromasil 100-C18 column was used with mobile phase consisted of acetonitrile （0.5％ TFA and 14 mmol/L formic acid amine solution， 2 ∶ 1，V/V）-acetonitrile （76 ∶ 24， V/V） at flow rate of 1.0 ml/min. The column temperature was room temperature， and detection wavelength was set at 215 nm. RESULTS： The liner range of MHD， LTG， PBB and OXC were 0.40-80.35， 0.41-81.10， 0.45-90.00 and 0.39-78.80 μg/ml， respectively （all r＞0.999 3， n＝7）. The extraction recovery was 54.09％-83.78％， and method recovery was 93.83％-113.25％. Both inter-day and intra-day RSDs were less than 13.51％. Other commonly used drugs didn’t affect the determination of component to be measured. CONCLUSIONS： The method is accurate， sensitive and specific， and spend less time. It can meet the demand of clinical drug monitoring.