Consumption of alcohol and tobacco, separately or jointly, can increase the risk of oesophageal squamous cell carcinoma (OSCC). It is unclear whether the amount of alcohol consumption by individual drinkers affects the joint carcinogenetic action of both agents. To demonstrate how the intensity of alcohol intake determines the risk of OSCC in relation to tobacco smoking, we conducted a multicentre case-control study. A total of 652 patients with pathology-proven OSCC, as well as 1127 gender, age, and study hospital matched controls were recruited. To identify a possible curvature in the continuous relationship between exposure and risk, we applied the generalised additive models to the collected data. Both non-drinkers who smoked tobacco and non-smokers who drank heavy alcohol (>30 g/day) were observed to have elevated cancer risks. A smoking habit-specific, non-linear increase in oesophageal cancer risk was recognised. Tobacco was found to interact with light-to-moderate alcohol (0.1-30 g/day) to increase the risk of oesophageal cancer in a supra-multiplicative way (Odds ratio (OR) ratio=5.5-5.7, p<0.05), whereas with heavy alcohol consumption in a simple multiplicative model (OR ratio=1.7-2.3, p>0.05). Weekly intake frequency had the strongest influence on the risk of neoplasm development. Alcohol consumption was responsible, respectively, for 18% and 77% of nonsmoking and smoking OSCC cases in this population. In conclusion, both light-to-moderate and heavy alcohol intake interact separately with tobacco in differently synergistic processes that can determine the development of this type of cancer.