Background: Breast cancer is the most common cancer among women, affecting 2.1 million women every year. Assessment of quality of life is considered the most important and strong indicator for breast cancer outcomes. The purpose of this study was to analyze biopsychosocial factors that affect the quality of life of breast cancer patients. Subjects and Method: A cross-sectional study was conducted in the breast cancer community in Surakarta, Central Java from December 2019 to January 2020. A sample of 200 breast cancer patients was selected by simple random sampling. The dependent variable was the quality of life of breast cancer patients. The independent variables were stadium, chemotherapy, length of diagnosis, age, depression, coping strategies, social networks, level of knowledge, education level, income level, employment status, and marital status. Quality of life was measured by WHO-QOL-BREF. Other data were collected by questionnaire. Data were analyzed by path analysis using the Stata 13 application. Results: The quality of life of breast cancer patients was directly increased by high family income (b= 3.27; 95% CI= 1.67 to 4.87; p<0.001), strong social network (b= 2.61; 95%CI= 0.96 to 4.26; p= 0.002), length of diagnosis ≥24 months (b= 2.68; 95% CI= 0.98 to 4.39; p= 0.002), good coping strategy (b= 1.65; 95% CI= 0.12 to 3.19; p= 0.034), and finished chemotherapy (b=1.32; 95% CI = -0. 22 to 2.87; p= 0.093). The quality of life of breast cancer patients was directly decreased by depression (b= -2.78; 95% CI=-4.41 to -1.15; p= 0.001) and advanced stage (b=-2.43; 95% CI= -4.04 to 0.83; p= 0.003). Quality of life was indirectly affected by coping strategy, marital status, chemotherapy, knowledge, length of diagnosis, age, employment, and education. Conclusion: The quality of life of breast cancer patients is directly increased by high family income, strong social network, length of diagnosis ≥24 months, good coping strategy, and finished chemotherapy. The quality of life of breast cancer patients is directly decreased by depression and advanced stage. Quality of life is indirectly affected by coping strategy, marital status, chemotherapy, knowledge, length of diagnosis, age, employment, and education. Keyword s : quality of life, breast cancer, path analysis Correspondence: Rizka Amalia Dewi. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java, Indonesia. Email: drizkaez@gmail.com. Mobile: +6282313121768. Journal of Epidemiology and Public Health (2020), 05(01): 119-131 https://doi.org/10.26911/jepublichealth.2020.05.01.12