Objective  To investigate the potential causal relationship between chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD) using a two-sample two-way Mendelian randomization (MR) approach. Methods  In the forward study, single nucleotide polymorphisms (SNPs) closely associated with CRS were selected as instrumental variables from publicly available genome-wide association studies datasets, with COPD as the outcome variable; conversely, in the reverse study, SNPs closely associated with COPD were selected as instrumental variables, with CRS as the outcome variable. MR analysis was conducted using three regression models: inverse variance weighted (IVW), MR-Egger regression analysis, and weighted median (WME) to assess the causal relationship between CRS and COPD. Cochran’s Q statistic, MR-Egger intercept, MR-PRESSO, and “leave-one-out” methods were employed to test for heterogeneity and horizontal pleiotropy, thereby evaluating the stability and reliability of the MR results. Results  A total of 14 SNPs closely associated with CRS were included in the forward study; the IVW-fixed effects analysis indicated that CRS may increase the risk of developing COPD [odds ratio=1.003, 95% confidence interval (1.002, 1.004), P<0.001], which was confirmed by the WME method, while the MR-Egger regression method did not show a causal link between CRS and COPD. Heterogeneity test (IVW result: Cochran’s Q=7.910, P=0.849; MR-Egger regression result: Cochran’s Q=7.450, P=0.827), MR-Egger intercept method (P=0.510), MR-PRESSO test (P=0.917), and “leave-one-out” method showed that the MR analysis results were reliable. In the reverse study, a total of 12 SNPs related to COPD were included as instrumental variables; MR analysis did not support the notion that COPD would increase the risk of CRS (P>0.05). Heterogeneity test (IVW result: Cochran’s Q=5.947, P=0.877; MR-Egger regression result: Cochran’s Q=5.937, P=0.821), MR-Egger intercept method (P=0.921), MR-PRESSO test (P=0.875), and “leave-one-out” analysis method showed that the MR analysis results were reliable. Conclusions  There is a potential causal association between CRS and COPD, and CRS may increase the risk of developing COPD. But there is no evidence to suggest that COPD increases the risk of CRS.