Malnutrition and reduced muscle strength are prevalent among patients with cancer and are both linked to impaired health-related quality of life (HRQoL). Although the individual impacts of these conditions are well documented, their combined effect remains insufficiently explored. This study aimed to examine how coexisting GLIM-defined malnutrition and low handgrip strength (HGS) affect HRQoL.

This-cross-sectional study (November 2024-June 2025) involved adult patients with cancer undergoing clinical treatment. Sociodemographic, clinical, lifestyle, and anthropometric information was collected. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria, and low HGS was used as a marker of reduced muscle strength. Coexistence was characterized by the simultaneous presence of malnutrition and low HGS. HRQoL was evaluated using the EORTC QLQ-C30 (0–100 scores), where higher functional scores indicate better HRQoL and higher symptom scores indicate greater symptom burden. Continuous variables were summarized as medians and interquartile ranges, and group differences were tested with nonparametric methods. Adjusted associations were examined using univariate general linear models, expressed as adjusted mean differences (Δ) and effect sizes (partial eta-squared, ({eta }_{p}^{2})). Statistical significance was set at p < 0.05.

After adjustment, low HGS showed significant and stronger associations with all functional scales and most symptom scales, whereas GLIM-defined malnutrition alone remained associated only with appetite loss. The coexistence of malnutrition and low HGS was associated with poorer physical (Δ = -35.1; p = 0.002; ({eta }_{p}^{2}) = 0.240), role (Δ = -40.3; p = 0.014; ({eta }_{p}^{2})= 0.216), and emotional functioning (Δ = -27.7; p = 0.044; ({eta }_{p}^{2}) = 0.125). Coexistence was also associated with higher levels of fatigue (Δ = 37.9; p < 0.01; ({eta }_{p}^{2})= 0.201), nausea and vomiting (Δ = 29.5; p ≤ 0.020; ({eta }_{p}^{2})= 0.209), pain (Δ = 36.0; p = 0.027; ({eta }_{p}^{2})= 0.134), dyspnea (Δ = 18.0; p = 0.042; ({eta }_{p}^{2})= 0.132), and appetite loss (Δ = 39.6; p = 0.015; ({eta }_{p}^{2})= 0.132).

The coexistence of GLIM-defined malnutrition and low HGS is associated with poorer HRQoL in patients with cancer, with low handgrip strength being particularly relevant to HRQoL impairment.