A higher platelet-to-lymphocyte ratio (PLR) has a clinical correlation with shorter survival in non-small cell lung cancer (NSCLC). The present study evaluated the association between the PLR and survival in patients with advanced NSCLC with malignant pleural effusion (MPE). Between January 2012 and July 2016, 237 patients with stage IV NSCLC were selected for evaluation. Receiver operating characteristic analysis was used to determine a cutoff for the PLR. Clinicopathological characteristics were compared between the high and low PLR groups, and the role of PLR as a predictive/prognostic maker was investigated. Among the 237 patients, 122 were assigned to the low PLR group and the other 115 to the high PLR group. According to multivariate analysis, male sex, not receiving active anticancer treatment, low hemoglobin level, low albumin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter overall survival (OS) (p = 0.010, <0.001, 0.011, 0.004, 0.003, and <0.001, respectively). In the subgroup multivariate analysis of driver mutation-negative NSCLC, high Eastern Cooperative Oncology Group score, not receiving active anticancer treatment, low hemoglobin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter OS (p = 0.047, <0.001, = 0.036, = 0.003, and <0.001, respectively). A high pretreatment PLR is independently associated with poor survival in stage IV NSCLC with MPE and in a subgroup of epidermal growth factor receptor and anaplastic lymphoma kinase wild-type NSCLC.