Objective: This study was conducted to evaluate the synergistic effect of cisplatin and interstitial KTP laser theapy induced hyperthermia in vitro and in vivo (interstitial laser chemotherapy, ILCT). Methods: In vitro study: human hypopharyngeal squamous carcinoma cell line (SNU-1041) was incubated in 1 mL of media containing various concentrations (0, 1, 2, 5, 10, 20, 50, 100 ng/mL) of cisplatin in 37° and 43°C for 2 hours. The viability of the cell was evaluated by MTT assay. In vivo study: human squamous cell carcinoma tumors were grown as subcutaneous transplants in nude mice and injected into tumor with cisplatin-epigel 100 μg, followed by interstitial laser therapy (ILT) via 0.6-mm diffuser fiber tips (532 nm, 1.0J/mm3). Results: In vitro study: the viability of tumor cells incubated with 10 ng/mL of cisplatin was 62% and 28% in 37°C and 43°C, respectively (p = 0.02). In vivo study: the tumor volume in 4 weeks after treatment was 179 mm3 in ILT group and 27 mm3 in ILCT group. The ILCT group showed 8 (80%) complete remission of tumors at 4 weeks follow up, while tumor remission occurred in only 3 (30%) in ILT group (p < 0.05). Conclusion: These results suggest ILCT may become an effective treatment for head and neck carcinoma with minimal functional deficit.