Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case-control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12-2.37), 2.09(95 % CI; 1.44-3.03) and 1.65(95 % CI; 1.15-2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02-4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37-7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09-6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10-1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.