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Background: Due to the high prevalence of breast cancer among women and its effects on personal and social life, it is important to detect effective factors on survival of these patients. This study was conducted to determine the factors affecting the survival of patients with breast cancer.Methods: This was a retrospective cohort study on 1077 patients with breast cancer referred to Seyed-al-Shohada hospital, Isfahan, Iran, between the years 1999 and 2010 and followed until 2014. Cox regression model were used to test the effects of various factors on the survival, log-rank test was carried out in the different categories of involved lymph nodes, and survival curves of these categories were plotted using Kaplan-Meier method. Analysis was done using SPSS software at the significance level of less than 0.050.Findings: The median of follow-up time was 5.5 years, and mean age of patient was 47.9 ± 11.3 years. 164 patients (15.2%) died during the follow-up period. The effect of the number of involved lymph nodes (P = 0.047) and cathepsin D (P = 0.009) was significant on the survival time of the patients. In patients with lymph node involvement between 3 and 10 (P = 0.031) and in patients with lymph node involvement of more than 10 (P = 0.030), risk of death was 3.02 and 3.08 times compared with patients without lymph node involvement, respectively. The log-rank test indicated a significant difference in survival between the different categories of involved nodes (P < 0.001).Conclusion: This study showed that the number of involved axillary lymph nodes and cathepsin D level associated with poor prognosis in survival of patients with breast cancer.