OBJECTIVE： To investigate the effects of UGT1A4 142T＞G polymorphism and blood concentration of valproic acid （VPA） on blood concentration of lamotrigine （LTG） in southern Chinese Han children with epilepsy， and to establish the prediction equation for quantitatively estimating blood concentration of LTG. METHODS： A total of 72 southern Chinese Han children with epilepsy selected from Guangzhou Women and Children’s Medical Center during Jan. 2010-Sept. 2016 were given LTG+VPA. LC-MS/MS and enzyme amplified immunoassay were adopted to determine the blood concentration of LTG and VPA. RFLP-PCR was adopted to determine UGT1A4 142T＞G polymorphism. The relationships of age， gender， blood concentration of VPA， UGT1A4 142T＞G polymorphism and LTG concentration-to-dose-ratio （CDR） were also investigate. The prediction equation for blood concentration of LTG was established by multiple linear regression analysis. RESULTS： Age and blood concentration of VPA were positively related to CDR of LTG （r＝0.225， 0.300，P＜0.05）； there was no statistical significance in the influence of gender on CDR of LTG （P＞0.05）. UGT1A4 TT， TG and GG genotypes were detected in 39， 29， and 4 cases respectively； the frequencies of each genotype were in line with the Hardy-Weinberg balance （P＞0.05）. CDR of LTG of TT genotype was significantly lower than those of TG and GG genotype， with statistical significance （P＜0.05）. Results of multiple linear regression analysis showed that the dose of LTG （x1）， body weight （x2）， blood concentration of VPA （x3） and UGT1A4 142T＞G polymorphism （x4） were all related to blood concentration of LTG （P＜0.05）. Using blood concentration of LTG （c） as dependent variable， above factors as independent variable， the regression equation was c＝0.794+0.032x1－0.057x2+0.010x3+0.532x4（R2＝0.616，P＜0.05； UGT1A4 TT genotype was equal to 0， TG and GG genotype was equal to 1）. There was a strong positive correlation between predicted blood concentration and measured ones （r＝0.785， P＝0.001）. CONCLUSIONS： The dose of LTG， body weight， blood concentration of VPA and UGT1A4 142T＞G polymorphism may associated with blood concentration of LTG. Established prediction equation can provide reference for precise medication in southern Chinese Han children with epilepsy.