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BACKGROUND/AIM The effect of oral trifluridine-tipiracil (TAS-102)-induced neutropenia on survival of patients with advanced/recurrent colorectal cancer was investigated. PATIENTS AND METHODS Between August 2014 and May 2016, 41 patients underwent TAS-102 monotherapy at Ogaki Municipal Hospital. Risk factors for survival were examined by univariate and multivariate analyses. RESULTS In 41 patients, mild neutropenia (grade 1-2) occurred in 10 patients (24.4%), severe neutropenia (grade 3-4) occurred in 13 (31.7%), and 18 (43.9%) did not experience neutropenia. The median overall survival times in the absent, mild, and severe groups were 120 days (95% confidence interval [CI], 67-179), 184 days (95% CI, 94-274), and 299 days (95% CI, 192-404), respectively (p = 0.045). In patients with severe neutropenia, the death hazard ratio was 0.442 (95% CI, 0.201-0.974; p = 0.042). CONCLUSION In patients with advanced/recurrent colorectal cancer, TAS-102-induced severe neutropenia was associated with superior survival.