Background/Aims: To investigate differences in blood routine indexes and the expression of cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) in malignant peritoneal mesothelioma (MPeM) and their relationship with clinical prognosis. Methods: We investigated changes in blood routine indexes between the MPeM patients and healthy subjects and detected the expression of COX-2 and NF-κB in peritoneal tissues by a streptavidin-peroxidase immunohistochemistry method. Potential prognostic factors were analyzed including age, gender, white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), COX-2, and NF-κB. Cox regression model analysis established independent factors for the survival prognosis of the patients. Results: Compared with the control group, AMC, MXD%, ANC, neutrophilic granulocyte percentage (NEUT%), APC, NLR, MLR, and PLR were markedly increased (p < 0.05) in the MPeM group. The positivity rates for COX-2 and NF-κB expression were 59.4 and 44.9%, respectively. Single factor analyses indicated that PLR, NLR, MLR, COX-2, and NF-κB were factors that affected the overall survival of MPeM patients, but multivariate analyses identified MLR and COX-2 as independent prognostic factors. Conclusions: High blood levels of MLR and COX-2 are adverse prognostic factors for patients with MPeM.