This meta-analysis investigated the relationship between non-steroidal anti-inflammatory drugs (NSAIDs) and lymph node/distant metastasis. Relevant sources were identified from MEDLINE, EMBASE, PubMed, and Cochrane Library. Studies that reported the odds ratio (OR)/risk ratio (RR)/hazard ratio (HR) with 95% confidence intervals (CIs) for the associations of interested outcomes were included. Pooled effect estimates were obtained by using random- or fixed-effect model depending on the heterogeneity across these studies. Sixteen studies involving 202780 participants, including prostate, breast, lung, and colorectal cancer patients, were included. Compared with the reference, generally patients exposed to NSAIDs at pre- and post-diagnosis experienced a significantly reduced risk of distant metastasis (RR 0.708, 95% CI 0.586-0.856 and RR: 0.484, 95% CI: 0.393-0.595, respectively), including prostate cancer (pre-diagnostic use: RR = 0.874, 95% CI, 0.787-0.97; post-diagnostic use: RR = 0.482, 95% CI 0.359-0.647), and breast cancer (pre-diagnostic use: RR = 0.644, 95% CI 0.565-0.735; post-diagnostic use: RR = 0.485, 95% CI 0.362-0.651). However, lymph node metastasis was weakly related with pre-diagnostic use of NSAIDs (RR = 0.949, 95% CI 0.914-0.985). NSAIDs are related to a significantly reduced risk of metastasis development, regardless of pre-diagnostic or post-diagnostic use. However, NSAIDs and lymph node metastasis are weakly associated. Our finding suggested a novel metastasis management.