This case report documents the diagnosis, treatment, and outcome of a nonresectable oral squamous cell carcinoma in a dog with initial poor prognosis. An approximately 4-year-old female Staffordshire Bull Terrier presented with a large mass on the front of lower jaw which was diagnosed as oral papillary squamous cell carcinoma by histopathology. CT scans revealed invasion of the cancer to the frenulum of the tongue. The mass was inoperable due to location, expansiveness, and metastatic lymph nodes. The dog received 4 treatments of intralesional hyaluronan-platinum conjugates (HylaPlat™, HylaPharm LLC, Lawrence, Kansas) at 3-week intervals. Clinical chemistry and complete blood count were performed one week after each treatment and results were within normal limits. Complications included bleeding due to tumor tissue sloughing, as well as a single seizure due to unknown causes. Upon completion of chemotherapy, CT showed that the mass had regressed and was no longer invading the lingual frenulum, and multiple lymph nodes were free of metastasis. The mass thus became resectable and the dog successfully underwent rostral bilateral mandibulectomy. Over one year after chemotherapy and surgery, the cancer remains in complete remission.