Goals of work Insomnia is the most common sleep disorder in patients with advanced cancer. The goal of this study was to investigate the relationship between insomnia and patient satisfaction with quality of life (QoL) in cancer. Materials and methods A case series of 954 cancer patients treated at Cancer Treatment Centers of America was investigated. Insomnia was measured using the EORTC QLQ-C30 insomnia subscale. Patient satisfaction with QoL was measured using the Ferrans and Powers Quality of Life Index (QLI). The relationship between insomnia and QLI was evaluated using multivariate analysis of variance and multiple regression analysis. Results Of 954 patients, 579 were females and 375 males, with the median age at presentation of 56 years (range, 20-90 years). Most common cancers were breast (26%), colorectal (19%), and lung (16%). After controlling for the effects of age and treatment history, every 10-unit increase in insomnia was statistically significantly associated with 0.67-, 0.17-, 0.42-, 0.20-, and 0.42-unit decline in QLI health/physical, social/economic, psychological/spiritual, family, and overall QoL functioning, respectively. Conclusions We found that insomnia is strongly correlated with patient satisfaction with QoL in cancer. Future studies should evaluate the impact of integrative cancer care services on patient satisfaction with QoL.