The aim of the current study was to investigate the relationship between nasopharyngeal carcinoma (NPC) and dry eye disease (DED) using the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was conducted, and patients with an NPC diagnosis were included. Next, one NPC patient was matched to four non-NPC participants via demographic data and systemic comorbidities. In total, 4184 and 16,736 participants were enrolled in the NPC and non-NPC groups, respectively. The primary outcome was the development of DED one year after the diagnosis of NPC. Cox proportional hazard regression was applied to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of DED. In this study, 717 and 2225 DED cases were found in the NPC and non-NPC groups, respectively, and the NPC group showed a significantly higher incidence of DED development compared to the non-NPC group (aHR: 1.45, 95% CI: 1.33-1.58, < 0.0001) in the multivariable analysis. The other covariates that were positively correlated with DED development included age over 40 years, an education level higher than senior high school, hypertension, DM, allergic pulmonary diseases, allergic otolaryngologic diseases, and allergic dermatological diseases (all < 0.05). In conclusion, the presence of NPC is an independent risk factor for subsequent DED.