Patients with malignancy were reportedly more susceptible and vulnerable to Coronavirus Disease 2019 (COVID-19), and witnessed a greater mortality risk in COVID-19 infection than noncancerous patients. But the role of immune dysregulation of malignant patients on poor prognosis of COVID-19 has remained insufficiently investigated. Here we conducted a retrospective cohort study that included 2,052 patients hospitalized with COVID-19 (Cancer, n = 93; Non-cancer, n = 1,959), and compared the immunological characteristics of both cohorts. We used stratification analysis, multivariate regressions, and propensity-score matching to evaluate the effect of immunological indices. In result, COVID-19 patients with cancer had ongoing and significantly elevated inflammatory factors and cytokines (high-sensitivity C-reactive protein, procalcitonin, interleukin (IL)-2 receptor, IL-6, IL-8), as well as decreased immune cells (CD8 + T cells, CD4 + T cells, B cells, NK cells, Th and Ts cells) than those without cancer. The mortality rate was significantly higher in cancer cohort (24.7%) than non-cancer cohort (10.8%). By stratification analysis, COVID-19 patients with immune dysregulation had poorer prognosis than those with the relatively normal immune system both in cancer and non-cancer cohort. By logistic regression, Cox regression, and propensity-score matching, we found that prior to adjustment for immunological indices, cancer history was associated with an increased mortality risk of COVID-19 (p < .05); after adjustment for immunological indices, cancer history was no longer an independent risk factor for poor prognosis of COVID-19 (p > .30). In conclusion, COVID-19 patients with cancer had more severely dysregulated immune responses than noncancerous patients, which might account for their poorer prognosis.