Recent preclinical studies have linked antidepressants (AD) to their potential anticancer effects in multiple cancers, but the impact on lung cancer remains unclear. This meta-analysis examined the associations between ADs and lung cancer incidence and survival. The Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by June 2022. We conducted a meta-analysis using a random-effects model to compare the pooled risk ratio (RR) and 95% confidence interval (CI) in those treated with or without ADs. Heterogeneity was examined using CochranQtest and inconsistencyI2statistics. The methodologic quality of the selected studies was assessed using the Newcastle-Ottawa Scale for observational studies. Our analysis, including 11 publications involving 1,200,885 participants, showed that AD use increased lung cancer risk by 11% (RR = 1.11; 95% CI = 1.02–1.20;I2= 65.03%;n= 6) but was not associated with overall survival (RR = 1.04; 95% CI = 0.75–1.45;I2= 83.40%;n= 4). One study examined cancer-specific survival. Subgroup analysis showed that serotonin and norepinephrine reuptake inhibitors (SNRIs) were associated with an increased lung cancer risk by 38% (RR = 1.38; 95% CI = 1.07–1.78;n= 2). The quality of selected studies was good (n= 5) to fair (n= 6). Our data analysis suggests that SNRIs were associated with an elevated risk of lung cancer, raising concerns regarding the use of AD treatment in patients vulnerable to lung cancer. The effects of ADs—particularly SNRIs—and their interplay with cigarette use and lung cancer risk in vulnerable patients merits further study.Significance:In this meta-analysis of 11 observational studies, we found evidence of a statistically significant association between the use of certain ADs and lung cancer risk. This effect merits further study, particularly as it relates to known environmental and behavioral drivers of lung cancer risk, such as air pollution and cigarette smoke.