Previous studies have indicated that influenza vaccination reduces the development of lung cancer. However, the protective effects of influenza vaccination on primary liver cancer in patients with chronic kidney disease (CKD) are unclear. This cohort study identified 12,985 patients aged at least 55 years who had received a diagnosis of CKD between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database of Taiwan. The patients were classified according to vaccination status. Propensity score matching was used to reduce selection bias. Cox proportional hazards regression analysis was used to evaluate the correlation between influenza vaccination and primary liver cancer in patients with CKD. The prevalence of primary liver cancer was lower in patients with CKD who had received an influenza vaccine (adjusted hazard ratio: 0.45, 95% confidence interval [CI]: 0.35–0.58, p < 0.001). The protective effects were observed regardless of sex, age, and comorbidities. Moreover, dose-dependent protective effects were observed. In the subgroup analysis, where the patients were classified by the number of vaccinations received, the adjusted hazard ratios for 1, 2–3, and ≥4 vaccinations were 0.86 (95% CI: 0.63–1.17), 0.45 (95% CI: 0.31–0.63), and 0.21 (95% CI: 0.14–0.33), respectively. In conclusion, influenza vaccination was associated with a lower incidence of liver cancer in patients with CKD.