Long-term cigarette smoke exposure damages the airway epithelium. However, the correlation among GSTM1 gene polymorphism, smoking status, and lung cancer susceptibility remains unclear. This study aimed to identify the genetic polymorphism of GSTM1 and examine the association of GSTM1 polymorphism and smoking history with lung cancer susceptibility. Methods? The genetic polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR) in 217 lung cancer patients and 198 controls. The demographic data and smoking history of the patients were collected. The age, sex, and residence of the two groups were also obtained. Results? Significant differences in GSTM1 polymorphism were observed between the case and control groups (P = 0.024). Smoking time and smoking index were significantly different between the case and control groups. With the increase in smoking time and smoking index, the differences became more obvious. There was a synergistic effect between GSTM1 and smoking (S = 3.35). The risk of developing lung cancer increased 4.82 fold in smokers carrying deficient-type GSTM1. Compared with patients carrying wild-type GSTM1, the risk of developing lung cancer was higher in those carrying deficient-type GSTM1 with the increase in smoking time and smoking index. In different pathological types, no significant differences were observed in GSTM1 polymorphism. In different pathological types, the proportions of patients increased with the increase in smoking time and smoking index, especially the proportion of patients with squamous cell carcinoma. Compared with wild-type GSTM1, the proportion of patients with deficient-type GSTM1 increased with the increase in smoking time and smoking index (P = 0.003 and 0.017). This trend was mainly observed in those with squamous cell carcinoma. Conclusion? GSTM1 mutation is associated with lung cancer susceptibility. Smokers carrying deficient-type GSTM1 are more likely to develop lung cancer. Compared with patients carrying wild-type GSTM1, smokers with deficient-type GSTM1 are more likely develop lung cancer when smoking time is more than 30 years and smoking index is more than 400. In patients carrying deficient-type GSTM1, the risk of developing squamous cell carcinoma increases with an increase in smoking time and smoking dose.