This study aimed to investigate physicians’ and nurses’ knowledge and attitudes toward advance directives (ADs) for cancer patients, which empower patients to take decisions on end-of-life needs if they lose their capacity to make medical decisions. A cross-sectional study was conducted using convenience sampling. The outcomes were responses to the knowledge and attitude questions, and the main outcome variables were the total scores for knowledge and attitudes toward ADs. This study included 281 physicians and nurses (60.5%). Most physicians were men (95, 80.5%), whereas most nurses were women (147, 86.5%). The mean (standard deviation; SD) total knowledge score was 6.8 (4.0) for physicians and 9.1 (3.0) for nurses (p < 0.001). There was a significant difference in the total knowledge score between nurses and physicians, with an adjusted mean difference of 1.54 (95% confidence interval [CI]; 0.08–2.97). Other significant independent predictors of knowledge of ADs were female sex (1.60, 95% CI; 0.27–3.13) and education level (master’s versus bachelor’s: 1.26, 95% CI; 0.30–2.33 and Ph.D. versus bachelor’s: 2.22, 95% CI; 0.16–4.52). Nurses’ attitudes appeared to be significantly more positive than those of physicians, and the mean total attitude score (SD) was 19.5 for nurses (6.2) and 15.1 (8.1) for physicians (p < 0.001). The adjusted mean difference (95% CI) for nurses versus physicians was 3.71 (0.57–6.98). All participants showed a high level of knowledge of ADs; however, nurses showed considerably more positive attitudes than physicians.