The present study examined the mediating role of anxiety, depression, sleepiness, insomnia, and sleep quality in the association between problematic social media use and quality of life (QoL) among patients with cancer. This cross-sectional survey study recruited 288 patients with cancer to respond to measures on anxiety, depression, sleepiness, insomnia, sleep quality, problematic social media use, and QoL. Structural Equation Modeling was used for the mediation analysis. There were significant relationships between all of the variables used in the study. It was revealed that problematic social media use did not directly influence the QoL of patients with cancer except via anxiety, depression, sleepiness, and insomnia. Sleep quality did not mediate the association between problematic social media use and QoL. Healthcare workers managing cancer should pay attention to the mental health needs of their patients even as they treat their cancer so as to improve their quality of life. Future studies may examine other variables that affect the QoL of patients with cancer as well as other mediating and moderating variables.