The authors' previous studies demonstrated that the major renal damage from hepatitis B virus infection is HBx‑induced apoptosis of renal tubular epithelial cells. Cordyceps sinensis is one of the most valuable of traditional Chinese medicines and is extensively used to treat chronic renal diseases. However, there is no research on the potential renal protective effect of C. sinensis on HBx‑induced apoptosis of renal tubular cells. The protective effect and underlying mechanism of C. sinensis were examined using a renal tubular epithelial cell line stably overexpressing HBx. HK‑2 cells were stably transfected with pCMV‑HBx to establish HBx‑overexpression in an in vitro cell model and HK‑2 cells transfected with an empty vector were generated as a control. The effect of C. sinensis on cell proliferation and apoptosis, the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway, and the enzyme activity of caspase‑3 and caspase‑9 was measured. The present study demonstrated that HBx transfection inhibited cell proliferation; increased apoptosis, caspase‑3 and caspase‑9 activity; and increased the activity of the PI3K/Akt pathway. Treatment with C. sinensis attenuated all of these HBx‑induced responses. HBx triggered apoptosis and activated the PI3K/Akt signaling pathway in HK‑2 cells. C. sinensis treatment significantly attenuated the effect of HBx, at least in part by suppressing the PI3K/Akt signaling pathway.