This is a phase I study of concurrent chemoradiation with pegulated liposomal doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and 9 with SCCHN were recruited in two phase I dose-escalation trials. The starting dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for 6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and 70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three chemoradiation delays of 7 days were confirmed. The median time of follow-up was 17.9 months (range 3-36 months). Four patients died due to local-regional failure combined with distant metastases (3 patients) and pericardial effusion (1 patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%), and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The incorporation of PLDH in concomitant chemoradiation regimens for future treatment of squamous cell carcinoma of the lung and head and neck is warranted.