BackgroundChemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinoma of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA. PurposeTo investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity. Material/methodsPatients were treated with RT and weekly cisplatin 40 mg/m2 between 1998–2020. Retrospective data from medical records (n = 65) and prospectively collected data from an observational study (n = 51) comprising physicianassessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2–4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. ResultsWe included 116 patients. T-stages were T1:4 %, T2: 71 %, T3: 17 %, T4: 8 % and 47 % has N + disease. RT doses were 53.75–64 Gy/45–51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77 % (95 %CI 68.7–84.5 %) and 86.4 % (95 %CI 78.3–91.7 %), respectively. Hospitalization occured in 20 % with 2.6 % being admitted due to febrile neutropenia. Hematological toxicty was low with 13.7 % grade 3 and 3.9 % grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild. ConclusionRT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile.