OBJECTIVES: The aim of this study was to analyse the association between tobacco consumption and Health-Related Quality of Life (HRQoL) in a general population on the basis of a representative panel dataset in Germany. METHODS: The analysis was designed as a cross-sectional study using the data of the “German Socio-Economic Panel Study” (SOEP) for the year 2006. The HRQoL was measured by the SF-12v2 (SOEP-Version with norm-based scores for all dimensions). For each of the eight subscores and both composite scores a separate multivariate linear regression analysis was conducted. RESULTS: Overall, 20,488 cases were included in the analysis. After the adjustment for age, sex, body-mass-index and duration of education there is a statistically significant association between consumption of tobacco and HRQoL in all subscores as well as both composite scores of the SF-12. The regression coefficients for current smoking (all non-smokers as reference group) are relatively small with -0.68 (role physical) to -1.35 (general health) points for physical domains and between -0.58 (vitality) and -1.47 (mental health) points for mental domains. These differences increase considerable for elderly persons (age of 50 or older, N = 9830) with - 1.274 (role physical) to -1.87 (general health) points for physical and -0.953 (vitality) to -1.682 (social functioning) for mental scales. Equally, there is a strong statistical association between the current amount of smoking (per 10 cigarettes per day) and HRQoL (-0.342 to -0.858 for physical and -0.47 to -1.07 for mental domains, N = 5560). CONCLUSIONS: In particular, the findings are limited by the inconclusive causality direction for smoking and mental health. However, these results confirm the existing evidence concerning the negative association between smoking status or smoking intensity and HRQoL in a general population.