Multidrug resistance (MDR) is a major cause of disease relapse and mortality in breast cancer. Paired‑related homeobox 1 (PRRX1) is associated with the epithelial‑mesenchymal transition (EMT), which is involved in tumor development, including cell invasion and MDR. However, the effect of PRRX1 on MDR had not clearly established. The present study investigated the influence of PRRX1 on MDR and the underlying molecular mechanisms in MCF‑7 breast cancer cells. MCF‑7 cells were divided into PRRX1+ group (cells transfected with a recombinant plasmid carrying the PRRX1 gene), negative control group (cells transfected with a blank vector) and blank group (untreated cells). It was found that the relative protein and mRNA expression levels of PRRX1, N‑cadherin, vimentin and P‑glycoprotein were significantly higher in PRRX1‑overexpressing MCF‑7 cells compared with those in control cells. The half‑maximal inhibitory concentration of three groups after treatment with docetaxel and cis‑platinum complexes were significantly higher in PRRX1‑overexpressing MCF‑7 cells compared with those in control cells. Furthermore, relative PTEN expression decreased significantly and levels of phosphorylated PI3K and AKT increased substantially in PRRX1‑overexpressing MCF‑7 cells. These results indicated that PRRX1 overexpression may induce MDR via PTEN/PI3K/AKT signaling in breast cancer. It is highly recommended that PRRX1 gene expression detection should be performed in patients with breast cancer to aid the selection of more appropriate treatments, which will lead to an improved prognosis in clinical practice.