Abstract: Objective To explore potential associations between three gasdermin B/sphingo-lipid biosynthesis regulator 3(GSDMB/ORMDL3) genes polymorphism with asthma risk and smoking behavior in Han population in Guangdong province of China.Methods A total of 394 asthma patients and 395 healthy physical examinees recruited from Affiliated Hospital of Guangdong Medical College were genotyped to detect single nucleotide polymorphism(SNP) of three GSDMB/ORMDL3 genes(rs7216389, rs4794820 and rs11650680) using SNaPshot technology.The correlations of gene polymorphism with asthma risk and smoking behavior were analyzed.Results The mean age of the asthma patients and healthy physical examinees was 45.37 and 45.23 years, respectively.There were no significant differences in age, gender and smoking status between the asthma patients and the healthy examinees.The variations in rs7216389 C/T and rs4794820 A/G genotype were significantly associated with increased asthma risk, with the odds ratio(OR) of 1.8 and 1.7(both P<0.0001);while the variation of rs11650680 C/T was significantly correlated with asthma risk(OR=0.8, P=0.1700).The frequency of rs7216389 T/T and rs11650680 C/C were higher among smoking asthma patients than among nonsmoking asthma patients, but the frequency of rs4794820 A/A was lower among the smoking asthma patients than among nonsmoking asthma patients significantly(P<0.0001 for all).Conclusion Our results show that rs7216389 C/T and rs4794820 A/G variations are associated with higher asthma risk and smoking could increases variation frequency in rs7216389 C/T, rs4794820 A/G, and rs11650680 T/C of GSDMB/ORMDL3 among Han population in Guangdong province of China.