Objective: This study aimed to investigate self-perceived burden (SPB) on families experienced by patients with cancer undergoing outpatient chemotherapy, and factors that affect SPB. Methods: Self-administered questionnaires were sent to patients with cancer in 17 designated cancer care hospitals. Of 1,981 effective responses (response rate 54.7%), 600 patients with cancer undergoing outpatient chemotherapy were included in this study. Results: More than 85% of participants reported SPB on their families. Multiple logistic regression analyses revealed independent physical and social factors that influenced the SPB on families among patients with cancer undergoing outpatient chemotherapy. Physical factor was recurrent or metastasized. Social factors were 40s or younger; living with families; marital history; worries of work or financial problems; worries of interpersonal relationship with families and others. Discussion and Implications: Our findings suggest that medical staff may need to offer psychological care according to patient’s cancer progression and support according to their social background to reduce SPB on their families.