Background: Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy accounting for 1-5% of intestinal tumors; however, its incidence has been increasing. Treatment for stage II and III anal canal SCC is infusional 5-fluorouracil associated with mitomycin and radiotherapy, since 1974. More convenient treatments for patients are needed. Methods:Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status, normal blood, and renal function were treated with capecitabine 825 mg/m2 12/12hs during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on day 1. Primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using Fleming single stage design. Results: From November/2010 to August/2013 42 patients were initially included, however 36 patients were assessed. Fifteen patients (41.7%) were stage II, 8 patients (22.2%) stage IIIA, and 13 patients (36.1%) stage IIIB. Four patients (11.1%) were HIV-positive, while 32 (88.9%) were HIV-negative. Thirty-two patients finished the treatment, 4 patients are still in treatment. Median follow-up was 18.7 months. Among patients who finished the treatment and were reevaluated at 6 months 4 patients (13.3%) presented partial response, 25 patients (83.3%) had complete response, and 1 patient developed liver metastasis (3.3%). Regarding grade 3-4 toxicities, 7 patients (21.8%) had grade 3 radiodermitis, 1 patient (3.1%) had grade 3 diarrhea, 2 patients (6.2%) had grade 3-4 thrombocytopenia, 3 (9.3%) had lymphopenia and one patient had grade 3 leukopenia. One HIV+ patient had septic shock, pneumonia, herpetic encephalitis and macrophage activation syndrome. Colostomy was required in 2 patients before the beginning of the treatment and 2 patients after the treatment because of local failure, corresponding to a colostomy rate of 12.5%. Conclusions: Capecitabine and mytomicin with radiotherapy seem to be a safe treatment for SCC of the anal cancer.