Febrile neutropenia frequently develops after chemotherapy, and the prompt administration of antimicrobial agents is required for treatment. In the present study, we searched for predictive factors for the failure of the initial antimicrobial agents used for febrile neutropenia (FN) in patients with lung cancer. Sixty FN patients treated in our ward from June 2005 to May 2011 were retrospectively analyzed. The definition of FN and the response to antimicrobial agents were determined by the Japanese guidelines. We divided the FN patients into two groups by their response to the initial antimicrobial agents. Next, the characteristics of the two groups were compared. The Multinational Association of Supportive Care in Cancer (MASCC) score did not differ between the two groups. The non-responder group demonstrated significant elevation of serum C-reactive protein (CRP) level. A multivariate analysis demonstrated that a CRP level higher than 10mg/dl is an independent risk factor for the failure of initial antimicrobial agents for FN with lung cancer (OR 11.0, 95% CI 1.635-74.5). When the CRP score was added to the MASCC score, the scoring system could more precisely predict the failure of initial antimicrobial agents in patients with lung cancer who developed febrile neutropenia.