Reducing lung cancer risk by modifying diet is highly desirable. We investigated whether different U.S. dietary patterns were associated with lung cancer risk. Dietary patterns were derived using exploratory factor analysis for 2139 non-small cell lung cancer (NSCLC) cases and 2163 frequency-matched controls. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Highest adherence (highest vs. lowest quintile) to the "Tex-Mex", "fruits and vegetables", and "American/Western" patterns was associated with a 55% reduced (OR = 0.45; 95% CI = 0.37-0.56; P < 0.001), 32% reduced (OR = 0.68; 95% CI = 0.55-0.85; P = 0.001), and 45% increased (OR = 1.45; 95% CI = 1.18-1.78; P < 0.001) risk of lung cancer, respectively. The effects were stronger for squamous cell carcinoma and ever smokers for the "fruits and vegetables" pattern, and stronger for other non-small cell lung cancer and never smokers for the "American/Western" pattern. Among six genome-wide association (GWA) studies-identified lung cancer susceptibility loci assessed, a variant (rs2808630) of the C-reactive protein gene modified the associations for the "fruits and vegetables" (P for interaction = 0.03) and "American/Western" (P for interaction = 0.02) patterns. Our study first showed that the "Tex-Mex" dietary pattern was associated with a reduced lung cancer risk. Also, the "fruits and vegetables" and "American/Western" patterns affected lung cancer risk, and the effects were further modified by host genetic background.