Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5–5.5 months (45–165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty-one cats with histologically confirmed oral SCC and T1-3N0M0 were treated with 10 once-daily fractions (Monday–Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow-up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression-free survival (PFS) was 105 days (1 year PFS of 23%), median local progression-free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.