Objectives To explore the association of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) with cancer-related fatigue (CRF) and quality of life (QOL) in cancer patients.Design A cross-sectional study.Settings A grade A tertiary hospital in Wuhan, China.Participants A total of 236 participants were recruited. Participants who were diagnosed with cancer received chemotherapy and/or radiotherapy, and aged ≥18 years were included in this study.Primary and secondary outcome measures The PLR, NLR and LMR were calculated based on the absolute lymphocyte count, neutrophil count, platelet count and monocyte count. The CRF and QOL of patients after the first chemotherapy/radiotherapy were evaluated.Results The median values (IQR) of PLR, NLR and LMR were 174.51 (126.14–261.02), 2.84 (1.64–5.24) and 2.56 (1.30–3.72), respectively. Univariate analysis indicated that high PLR (≥ 174.51), high NLR (≥ 2.84) and low LMR (< 2.56) at baseline significantly correlated with CRF and poor QOL after the first chemotherapy/radiotherapy (p