Aims: Management of locally advanced oral squamous cell carcinoma (LAOSCC) is challenging due to the risk of functional and aesthetic impairment after radical surgery. Induction chemotherapy (ICT) may reduce tumor burden and facilitate organ preservation in selected patients. This study aimed to evaluate the efficacy, safety, and feasibility of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy (TPF-ICT) for LAOSCC. Methodology: We retrospectively reviewed six patients with LAOSCC treated with TPF-ICT between April 2021 and March 2024. The regimen consisted of docetaxel (75 mg/m²), cisplatin (75 mg/m²), and 5-fluorouracil (750 mg/m², day1-5) every 3 weeks. Tumor response was assessed using RECIST v1.1, and toxicities were graded according to CTCAE v5.0. All patients proceeded to definitive therapy following ICT. Overall survival (OS) and progression-free survival (PFS) were analyzed. Results: The objective response rate was 100%, with all patients achieving a partial response. All patients transitioned to definitive therapy (surgery, n=2; chemoradiotherapy, n=4) without delay. In surgical cases, pathological evaluation demonstrated remarked treatment effects. The median OS was not reached, while the median PFS was 10.0 months (95% CI: 8.0–NE). Grade 3/4 neutropenia occurred in all patients but was manageable with appropriate supportive care. Non-hematologic toxicities were generally manageable, and no treatment-related deaths or discontinuations were observed. Conclusions: TPF-ICT demonstrated a high response rate and acceptable feasibility in patients with LAOSCC. This approach may facilitate definitive therapy and potentially contribute to functional preservation. Despite frequent neutropenia, the regimen was manageable with appropriate supportive care.