Background 5-hydroxytryptamine 2A receptor (5-HT2A) gene has been regarded as a candidate gene for susceptibility to schizophrenia. In particular, the 5-HT2A receptor has received much attention because it demonstrates to be an important site of action of atypical antipsychotic agents to alleviate negative symptoms. The current study investigated whether the 5-hydroxytryptamine 2A receptor (5-HT2A) gene T102C polymorphism was associated with treatment response to risperidone in the first episode Chinese patients with schizophrenia.Methods 201 first episode Chinese Han patients with schizophrenia were given risperidone for up to 56 days.Genotyping of 5-HT2A gene T102C polymorphism were performed by using PCR-RFLP. The Positive and Negative Symptom Scale (PANSS) was used for the evaluation of the severity of psychotic symptoms before and after 8 weeks treatment with risperidone.Results 5-HT2A receptor 102 -T/T genotype was significantly associated with both the PANSS total and negative syndrome subscale scores before treatment, and with the reduction rates in both the PANSS total and negative syndrome subscale scores after eight weeks risperidone treatment.Conclusions The results suggest that 5-HT2A T102C A/A1 genotype subgroup influences individual response to risperidone in first-episode Chinese patients with schizophrenia.