Objective: To investigate the factors affecting the quality of life of cancer patients by examining the degree of the COVID-19 pandemic-related depression, anxiety, stress, and treatment crisis. Methods: Data were collected from 132 cancer patients undergoing surgery, chemotherapy, radiotherapy, and hormone therapy at K University Hospital in D City using a structured questionnaire. The period of data collection was from May 6 to May 28, 2022. The collected data were analyzed using descriptive statistics, t-test, ANOVA, Pearson’s correlation, and stepwise multiple regression. Results: The mean scores of quality-of-life, depression, anxiety, stress, and treatment crisis during the COVID-19 pandemic were 84.64 ± 29.09, 15.14 ± 6.49, 4.66 ± 5.27, 75.83 ± 17.70, and 78.52 ± 19.95, respectively. In terms of factors affecting the quality of life related to the COVID-19 pandemic, COVID-19 pandemic-related stress (β = 0.41, P < 0.001) appeared to have the greatest impact, followed by COVID-19 pandemic-related treatment-crisis (β = 0.28, P = 0.002), anxiety (β = 0.21, P = 0.002), and gender (β = 0.14, P = 0.009), with a total explanatory power of 67.6%. Conclusion: To improve the quality of life during the COVID-19 pandemic, COVID-19 pandemic-related stress, treatment-crisis, and anxiety should be periodically monitored and nursing interventions such as education on infection prevention, management, and emotional support programs should be provided to decrease the COVID-19 pandemic-related stress, treatment-crisis, and anxiety.