Objective:To analyze the relationship between plasma D-dimer level and cancer-related fatigue and quality of life in patients with lung cancer after chemotherapy.Methods:A cross-sectional study was conducted involving 58 patients with stage ⅠB-ⅢA lung cancer who received chemotherapy at The First Hospital of Anhui University of Science and Technology from January 2020 to December 2023. These patients comprised the observation group. The control group consisted of 41 patients diagnosed with lung cancer who had completed adjuvant chemotherapy and entered the follow-up stage. The plasma D-dimer level in the observation group was monitored before and after four cycles of postoperative adjuvant chemotherapy. The plasma D-dimer level in the control group was monitored before and after 3 months of follow-up. The Chinese version of the Cancer Fatigue Scale and the Chinese version of the Functional Assessment of Cancer Therapy-Lung (FACT-L) were used to evaluate cancer-related fatigue levels and quality of life in both groups. Pearson correlation analysis was performed to assess the relationship between plasma D-dimer levels and cancer-related fatigue and quality of life.Results:After four cycles of chemotherapy and 3 months of follow-up, the plasma D-dimer level in the observation group was significantly higher than that in the control group [(1.17 ± 0.32) mg/L vs. (0.66 ± 0.29) mg/L, t = -8.26, P < 0.001]. The score of the Chinese version of the FACT-L in the observation group was significantly higher than that in the control group [(79.82 ± 9.74) points vs. (67.49 ± 8.12) points, t = -6.85, P < 0.001]. The scores for tumor-related symptoms, physiological status, social/family status, functional status, and emotional status in the FACT-L for the observation group were (21.26 ± 3.17) points, (14.37 ± 2.24) points, (22.63 ± 3.48) points, (11.53 ± 2.13) points, and (14.79 ± 2.73) points, which were significantly lower than those in the control group [(22.42 ± 3.31) points, (17.65 ± 2.64) points, (25.12 ± 3.39) points, (16.34 ± 2.68) points, (16.37 ± 2.76) points, t = 3.26, 6.48, 3.56, 3.60, 2.82, all P < 0.05]. Pearson correlation analysis revealed that the plasma D-dimer level was positively correlated with the cancer-related fatigue score ( r = 0.367, P < 0.001) and negatively correlated with the total FACT-L score ( r = -0.334, P < 0.001). Conclusion:In patients with stage ⅠB-ⅢA lung cancer after surgery, changes in plasma D-dimer levels during adjuvant chemotherapy are associated with the degree of cancer-related fatigue and affect quality of life. Therefore, monitoring plasma D-dimer levels can provide important reference value for assessing the outcome of chemotherapy and guiding clinical treatment.