BACKGROUND: Esophageal second primary neoplasms (ESPNs) are common in hypopharyngeal squamous cell carcinoma (HPSCC) patients and are associated with poor prognoses. The effectiveness of image-enhanced endoscopy (IEE) has not been well established. METHODS: We reviewed the patients between April 2016 and April 2018 with HPSCC receiving ESPNs screening via white-light imaging, narrow-band imaging, and Lugol chromoendoscopy. RESULTS: Of 99 eligible patients, ESPNs prevalence was 31%. Of the 69 patients assigned to the follow-up group, 23 with positive findings showed significantly increased previous histories of second primary malignancies in the upper aerodigestive tract. Among them, patients without symptoms at the time of IEE screening showed less advanced T stages and higher percentages of receiving minimal invasive therapy. CONCLUSION: The present study represented the clinical utility of routine IEE screening in HPSCC patients and proposed routine surveillance may help identify and properly manage early-stage ESPN.