Breast cancer is one of the most common malignant diseases affecting women, and chemotherapy is a main treatment option. However, it can cause various side effects that impact patients’ quality of life. Poorly managed chemotherapy side effects may affect patients’ physical, psychological, social, and environmental well-being. This study aimed to analyze the relationship between chemotherapy side effects and the quality of life of breast cancer patients in the Chemotherapy Unit of Raden Mattaher Regional Hospital, Jambi. A cross-sectional design was used with total sampling involving 92 breast cancer patients undergoing chemotherapy. Data were collected using a chemotherapy side effects questionnaire and the WHOQOL-BREF instrument. Data analysis included univariate and bivariate analysis using Kendall’s tau-b test. The results showed that most respondents were aged 46–55 years (39.1%), had a high school education (44.6%), were unemployed (83.7%), were in stage III (60.9%), and were undergoing the 5th chemotherapy cycle (26.1%). The majority experienced adaptive chemotherapy side effects (56.6%) and had a good quality of life (45.7%). Statistical analysis revealed a significant relationship between chemotherapy side effects and quality of life (p-value = 0.000). In conclusion, chemotherapy side effects are significantly associated with the quality of life of breast cancer patients. Health professionals are encouraged to provide better support and education in managing chemotherapy side effects to maintain and improve patients’ quality of life.