Background Diabetic foot ulcer (DFU) is a serious and costly complication in diabetes which affects approximately 15% of patients with diabetes and affects their quality of life (QOL). Objectives The purpose of this study was to investigate the factors associated with QOL in patients with DFU. Patients and Methods This cross-sectional study was performed on 60 patients (32 males and 28 females) hospitalized for DFU, performed through convenience sampling. Data related factors and the QOL questionnaire for patients with DFU were abridged. This questionnaire has 29 questions in six dimensions of enjoying life, physical health, daily activities dependence, negative emotions, concern about wound, and wound caring, which evaluate the QOL in patients with DFU. The scoring method for this tool is five optional Likert. Descriptive and analytic statistical methods were used to analyze the data. Results Of the 60 patients with DFU, 53% were male and 47% female with an average age of 58.08 ± 11.95 years and average QOL of 41.1 ± 9.15. Statistical analysis showed that age (P = 0.002), employment (P ≤ 0001), socioeconomic status (P = 0.016), leg ulcer (P ≤ 0001), and the number of foot ulcer (P = 0.017) had a statistically significant relationship with QOL and its dimensions. Other variables did not have a significant relationship with QOL, but some of them such as smoking during negative emotions (P = 0.046) and marital status affecting the foot care difficulties (P = 0.03) had significant statistical relationships with QOL. Conclusions Diabetic foot ulcer affects different aspects of life and can reduce patient’s QOL. To improve the care behaviors and have a better control of foot ulcers and improve the QOL for these patients, taking into account factors such as age, occupation, marital status, number of wounds, and economic status is essential to plan for care and health needs in these patients.