Background and Objective To preserve cardiovascular health in persons with spinal cord injury (SCI), it is important to promote physical activity programs adapted to them. Home-based exercise programs allow patients to perform clinician-prescribed physical activity without going to a hospital. However, they make it difficult for the clinician to guide and monitor the patient. To face this issue, this paper proposes a novel smartphone-based mobile application (Fisiofriend), and evaluates its feasibility with a pilot study in a real clinical intervention. Methods Fourteen SCI male subjects were involved in a 6-weeks home-based intervention, based on upper limbs exercises: 7 subjects (APP group) used Fisiofriend, and 7 subjects used traditional pictorial instructions on paper (PAPER group). At the beginning (t1) and end (t2) of the study period, we measured: (i) biceps and triceps brachii strength and endurance parameters with an isokinetic dynamometer (Biodex System 4), (ii) O2 maximal consumption with a crank ergometer stress test (VO2000, Medgraphics). Moreover, we collected subjective data about subjects’ perception of the support (app or paper) in the home-based program. Results Physiological results were encouraging for both groups. Questionnaire data suggests a possible advantage of the app in terms of pleasantness, engagement and perception of positive effects. Practical clinical experience with the subjects and their informal reports highlighted which features of the app could be of particular benefit in real interventions, as we discuss in the paper. Conclusions The study showed the feasibility of using a mobile app in home-based exercise programs involving SCI patients. We discuss implications of introducing such kind of apps into clinical practice.