Abstract Background Post-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC. Methods We retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records. Results Two-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence. Conclusions Positive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.