Background The use of Web‐based technology to facilitate self‐care and communication with health care providers has the potential to improve psychosocial outcomes for patients undergoing cancer treatment. This study reports an analysis of psychosocial outcomes of the electronic self‐report assessment for cancer study. Methods Adult patients starting cancer therapy were randomized to receive usual education about symptoms and quality of life topics (control) or usual education plus self‐care instruction for symptoms and quality of life issues, communication coaching, and the opportunity to track symptoms and quality of life between clinic visits (intervention). Depression (Patient Health Questionnaire‐9) and social, emotional, and role functioning (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 subscales) were measured before treatment (T1), 3 to 6 weeks after starting treatment (T2), 2 weeks later (T3), and 2 to 4 weeks after treatment ended or at the next restaging visit for participants who continued to receive treatment (T4). Clinicians received summaries of participant reports at each time point in both groups. Results In multivariable analysis, the depression scores were significantly lower (P = .04) and there was a trend to higher social and role functioning (P = .07) in the intervention group compared with the control. Working status was significantly associated with lower depression and better social and role functioning. Conclusions A patient‐centered, Web‐based intervention that facilitates self‐care and communication can improve psychosocial outcomes in the cancer setting.