Background: In patients with advanced cancer receiving immune checkpoint inhibitors (ICIs) therapy, there are conflict perspectives about the influence of concomitant use of proton pump inhibitors (PPIs). We are aimed at exploring the influence of concomitant PPIs exposure on clinical outcome among cancer patients receiving ICIs treatment. Methods: We searched relevant literatures in PubMed, EMBASE, and the Cochrane Library without language restrictions. We extracted the data from selected studies and calculated the pooled hazard ratios (HRs) with 95% confidence intervals (CIs) through professional software for overall survival (OS) and progression free survival (PFS) among cancer patients undergoing ICIs therapy exposed to PPIs. Results: Fourteen studies including 6716 advanced cancer patients receiving ICIs treatment were appropriate for analysis judging by pre-set inclusion and exclusion criteria. The result indicated that concomitant PPIs exposure was significantly related to shorter OS (HR 1.388; 95%CI:1.278-1.498, P<0.001) and PFS (HR 1.285;95%CI:1.193-1.384, P<0.001) among multiple cancer patients receiving ICIs therapy. Conclusions: Our meta-analysis showed that concomitant PPIs exposure had adverse impact on clinical outcome among patients receiving ICIs therapy. Clinical oncologists must be cautious of PPIs delivery during ICIs treatment.