Drug resistance is a principal contributor to the poor prognosis of ovarian cancer (OC). Therefore, identifying factors that affect drug resistance in OC is critical. In the present study, 51 OC specimens from lab collections were immunohistochemically tested, public data for 489 samples from The Cancer Genome Atlas cohort and 1,656 samples from the Kaplan‑Meier Plotter were downloaded, and data were retrieved from Oncomine. It was identified that the mRNA and protein expression of the potassium calcium‑activated channel subfamily N member 3 (KCNN3) was markedly lower in OC tissues compared with normal tissues, and in drug‑resistant OC tissues compared with sensitive OC tissues. Low KCNN3 expression consistently predicted shorter disease‑free and overall survival (OS). Specifically, low KCNN3 expression predicted shorter OS in 395 patients with low expression levels of mucin‑16. There was additional evidence that KCNN3 expression is mediated by microRNA‑892b. Furthermore, text mining and analyses of protein and gene interactions indicated that KCNN3 affects drug resistance. To the best of the authors' knowledge, this is the first report to associate KCNN3 with poor prognosis and drug resistance in OC. The present findings indicated that KCNN3 is a potential prognostic marker and therapeutic target for OC.