Background and aims Oral nutritional supplements (ONS) are considered a cornerstone in the treatment plan of malnutrition in cancer patients. However, the prevalence of inappropriate prescription of ONS is high. In this study, we aim to investigate the effect of inappropriate oral nutritional supplementation (consisting of prescription of ONS without evident clinical indication, or the absence of ONS when at risk of malnutrition) on the quality of life of cancer outpatients. Methods A cross-sectional comparative study was conducted in 104 cancer outpatients, receiving ONS without prior malnutrition risk screening (n = 51), and patients not receiving ONS (n = 53). Nutritional risk screening was performed using the abridged patient-generated subjective global assessment (ab-PG-SGA). The quality of life was assessed using EORTC QLQ-C30 version 3.0 questionnaire. Multivariate analysis was conducted to determine the predictors of quality-of-life scales. Age (years), malnutrition (ab-PG-SGA scores), BMI (kg/m2), TSF (mm), MUAC (cm), ONS (yes, no) were entered into the linear regression analysis as predictors (backward stepwise linear regression analysis). Results The prevalence of malnutrition risk (ab-PG-SGA ≥ 6) was 74%. The median score of the ab-PG-SGA for ONS receiving group was significantly higher (p = 0.045). Furthermore, univariate analysis showed that the scores of the global health status (QoL) and the role functioning (RF) scales were significantly lower for the ONS receiving group (p = 0.020 and p = 0.016, respectively). Multivariately, malnutrition, inappropriate ONS prescription, and triceps skin fold were found to be predictors of the RF scale, while malnutrition was the only predictor for the QoL. Conclusion The inappropriate ONS prescription does not improve nutritional status or quality of life of cancer outpatients.