Cancer is a serious threat to public health and the economy worldwide. Statistical data from the World Health Organization (WHO) in 2018 have demonstrated that lung cancer is the most commonly diagnosed cancer (11.6％ of the total cases) and the leading cause of cancer death (18.4％of the total cancer deaths), closely followed by gastric cancer (5.7％ and 8.2％), and liver cancer (4.7％ and 8.2％)[1]. The situation is similar for these three types of cancer in the Hubei province of China[2]. Interleukin-22 (IL22), a member of the IL-10 family, is regarded as a link between inflammation and cancer. Recent studies have shown that IL22 acts as a tumor promoter and may promote carcinogenesis rather than function in antitumor immunity[3]. Interestingly, evidence of IL22 involvement in carcinogenesis manifests as dysregulation of IL22 expression in patients with many common cancers, including those of the stomach, liver, lung, stoma gut, and skin[4]. Therefore, it is hypothesized that individuals carrying certain genetic variants in the IL22 gene are vulnerable to the challenge of dysimmunity and are more susceptible to cancer. To test this hypothesis, we adopted a two-stage case-control approach to explore the potential contribution of IL22 gene promoter polymorphisms to cancer susceptibility in a Chinese Han population of Hubei province, and further elucidated the specific mechanism underlying the contribution of associated polymorphisms to cancer susceptibility.