As reported by the Taiwan Cancer Registry in 2013 squamous cell carcinoma of head and neck cancer (HNSCC) was the sixth most frequently diagnosed cancer and the 5th most common cause of cancer related death and its incidence and mortality rate is still rising. The co-occurrence of HNSCC and secondary primary cancer (SPC) and the chemopreventive effect of aspirin on certain malignancies had been reported. Therefore we conducted this national study to investigate the use of aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer in Taiwan. We searched the Registry for Catastrophic Illness in the National Health Insurance Research Database (NHIRD) for 18,234 patients (3,576 aspirin users and 14,667 non-aspirin users) diagnosed with HNSCC during 2000–2005. The SPC incidence density during follow-up in 2000–2011 was compared between the groups. For HNSCC patients, aspirin use after diagnosis was significantly associated with SPC risk reduction by 25% (adjusted HR, 0.75; 95% CI, 0.63–0.89; p = 0.001) after multivariate analysis. In the subgroup analysis, we found that esophageal cancer and stomach cancer incidence were significantly reduced after aspirin use (adjusted HR, 0.60; 95% CI, 0.41–0.90; p = 0.01 for esophageal cancer; adjusted HR, 0.27; 95% CI, 0.08–0.87; p = 0.03 for stomach cancer). Aspirin use for 1–3 years was associated with SPC risk reduction by 35% (adjusted HR, 0.65; 95% CI, 0.49–0.87; p = 0.003). SPC risk reduction extended continuously for more than 3 years of follow up (adjusted HR, 0.72; 95% CI, 0.53–0.98; p = 0.030). Our data shows aspirin use was associated with reduced SPC incidence for HNSCC patients, attributed mainly to reduced risk of esophageal and stomach cancer.