Background: Squamous cell carcinomas of the upper aero-digestive tract (UADTSCC) are a multifaceted public health problem. Effects of lifestyle risk factors, including tobacco (chewing and smoking), alcohol drinking and exposure to second hand tobacco smoke (SHS) at home and their association with UADT cancers was assessed in a case-control study with a life-course perspective. The study was conducted at two different hospitals in Pune, India. Material and methods: The total sample size (N=480) included 240 histopathologically confirmed cases of UADT cancers and an equal number of controls frequency matched with cases by gender and age distribution (+5 years). All the patients were interviewed face-face using structured questionnaires. Self-reported information on socio-demographic and lifestyle risk factors from childhood to the date of diagnosis of disease/cancer was obtained. Frequency, duration and age of initiation of habits were also recorded to study dose-response relationships. Odds ratios and their 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. Results: Chewing tobacco emerged as the strongest predictor for UADT cancers (OR=7.61; 95% CI 4.65-12.45) in comparison to smoking and drinking alcohol. Exposure to SHS during childhood (Conclusions: Early exposure to various modifiable lifestyle risk factors has a strong positive association with UADT cancer incidence. Effective future public health interventions with focus on vital time points in life targeting these risk factors could possibly be a major step in primary prevention and control of this cancer at the population level.