Gender and sex differences affect women with kidney failure (KF) negatively at all stages of the disease. This study assessed gender differences in self-care, hemodialysis symptoms, and quality of life in a sample of 102 adult KF patients treated with hemodialysis, from two clinical centers in Mexico. Self-care agency, quality of life, and the symptoms related to hemodialysis were evaluated through questionnaires, and sociodemographic and laboratory variables were obtained from the clinical records. Compared to male patients, female patients reported similar self-care, lower quality of life subscales (symptoms, physical functioning, pain, and overall health), and higher prevalence and intensity of hemodialysis symptoms. There were gender differences regarding the correlation between self-care and quality of life, symptoms intensity, and symptoms prevalence. In conclusion, women with KF treated with hemodialysis perceived a higher impact of hemodialysis and reported a lower quality of life than men. Despite having a similar self-care agency, the self-care correlations with quality of life and hemodialysis symptoms appeared different between men and women treated with chronic hemodialysis. Such differences may be important in future nursing interventions to improve self-care and quality of life among KF patients.