Background: The novel coronavirus infectious disease (COVID-19) is an international concern as it spreads through human populations and across national and international borders. Methods: In this retrospective study, we consecutively included all cancer patients who had been identified as having a nucleic acid-confirmed COVID-19 from two designated hospitals in Wuhan, China. COVID-19 patients without cancer were also enrolled for comparison. The clinical data were gathered from the medical records from Jan 14 to March 12, 2020. Results: Among the 117 cancer patients diagnosed with COVID-19, the median age was 63 years and 48.7% were male. Male sex, hematologic cancer, dyspnea on admission, and anti-cancer therapies were associated with an increased risk of mortality in cancer patients with COVID-19. We found that elevated levels of TNF-alpha, IL-2R, IL-6, and IL-8 were associated with a poorer prognosis in cancer patients with COVID-19, but no statistically significant association was found in patients without cancer. In addition, IL-2R and IL-6 markedly decreased in cancer patients who recovered from COVID-19. However, lymphocyte subsets were diminished in cancer patients who died from COVID-19, including total T cells, total B cells, helper T (Th) cells and suppressor T (Ts) cells. Conclusions: Cancer patients with COVID-19 were associated with high mortality (23.9%). A decrease in lymphocyte subsets and higher levels of cytokines were associated with a higher risk of severe outcome and could be utilized as the reference index to predict the survival outcome of cancer patients with COVID-19.