Background With the increase of the number of smokers, tobacco exposure among pregnant women is becoming more and more common. Though that pregnant women exposed to first-hand smoke and second-hand smoke are susceptible to physiological and psychological health issues has been proved in previous studies, there are no enough studies focus on the impact of third-hand smoke. This study aimed to assess and compare health-related quality of life for pregnant women with exposure to first-hand smoke, second-hand smoke, third-hand smoke and non-exposure to tobacco in mainland China. Methods National-based cross-sectional study is based on a questionnaire survey which collects information including demographics, smoking behaviors and self-evaluation. All questionnaires were delivered and collected from August to September 2019. EuroQol group’s visual analog scale and EuroQoL Five-dimension Questionnaire were used to collect data in mainland China. Results Totally, 15682 pregnant women were included in this study, among which non-exposure to smoke were 7564 (48.2%), exposed to first-hand smoke, second-hand smoke and third-hand smoke were 89 (0.6%), 2349 (15.0%), and 5680 (36.2%) respectively. Pregnant women without tobacco exposure had the highest EuroQol group’s visual analog scale score (mean value=85.4[SD=14.0]), while those with first-hand smoke had the lowest score (mean value=77.4[SD=22.2]). Among all five dimensions of EuroQoL Five-dimension Questionnaire, there were significant differences of EQ-index among groups with different tobacco exposure in usual activity and anxiety or depression dimensions (p<0.001). Conclusions Third-hand smoke exposure had close relationship with low health-related quality of life in pregnant women. Moreover, second-hand smoke exposure significantly led more problems on mental dimension of pregnant women.