Abstract Protective effect of garlic on the development of cancer has been reported in the in vitro and in vivo experimental studies; however, few human epidemiologic studies have evaluated the relationship. A population-based case–control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was used to estimate adjusted ORs and their 95% confidence intervals (CI), and to evaluate ratio of ORs (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44–0.72) with a monotonic dose–response relationship (Ptrend < 0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking [synergy index (SI) = 0.70; 95% CI, 0.57–0.85; and ROR = 0.78; 95% CI, 0.67–0.90], as well as high-temperature cooking oil fume (ROR = 0.77; 95% CI, 0.59–1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose–response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation. Cancer Prev Res; 6(7); 711–8. ©2013 AACR.