Background: Establishing appropriate communication with cancer patients is necessary to make decisions for them and involve them in the care process to prevent the adverse consequences of cancer treatment. Thus, the qualitative study on the challenges experienced by oncology nurses can lead to a better understanding of these challenges and help these nurses acquire advanced communication skills. Objectives: This study was conducted to explain the communication challenges experienced by oncology nurses during providing care to cancer patients by applying a qualitative content analysis approach. Methods: This qualitative study was conducted with the participation of 18 nurses who were selected by the purposive sampling method, working in the oncology departments of Iran’s hospitals in 2021. Semi-structured interviews were held for data collection. After transcribing the interviews, data analysis was performed using the Granheim and Landman (2004) method. The MAXQDA software (2020) was used for data management. The criteria proposed by Lincoln and Guba were used to assure data accuracy and reliability. Results: Thirty subcategories, eight categories, and four themes were extracted following data analysis. The themes included the nurse’s close relationship with cancer patients as a double-edged sword, curvy and sinusoidal professional communication for oncology nurses, relationship with an opposite-gender patient as a missing factor in nursing care, and marginalization of relationships during the coronavirus pandemic. Conclusions: Nurses’ challenges in communicating with cancer patients can be reduced by improving their communication skills via various strategies, including empowering nurses by employing cognitive empathy and using communication models such as the Comfort model.