Osteosarcoma (OS) typically occurs during puberty. The one-year treatment for OS can be very challenging. However, little empirical research has explored the experiences of adolescents with OS. This research explored the experiences of Taiwanese adolescents with OS, utilizing a qualitative inductive content analysis with in-depth interviews and field notes that captured interviewer observations. In total, 20 participants—aged between 10 and 19 years and being treated for OS—were recruited. Ten categories were extracted: disbelief, hope for recovery and maintaining body integrity, experience with physical symptoms, inappropriate sleep hygiene, experience of psychosocial distress, use of spirituality to recover from misfortune, information acquisition, preparation to return to school, interdependence, and dedication to hope of recovery. This is the first empirical qualitative study to explore the experiences of Taiwanese adolescents with OS during treatment since being diagnosed. Close surveillance of the compliance in rehabilitation and physical function is needed. Providing age-appropriate and culture-oriented support systems would be helpful for addressing their psychosocial difficulties. Social networking sites closely moderated by health professionals may be a feasible way enhancing psychosocial well-being. Conducting a descriptive exploratory qualitative study for further development of psychosocial supportive care interventions is recommended.