DC-DC modular multilevel converter (DC-DC MMC) is an attractive candidate for high-voltage DC (HVDC) interconnections since it can provide the required voltage matching, galvanic isolation and flexible power control abilities. The semiconductor loss of such a DC-DC MMC is a major concern for both system evaluation and parameter design. However, it cannot be measured directly since it is out of the precision range of the high-voltage measuring equipment, and thus, mathematical analysis is considered as a feasible alternative. This paper proposes an accurate off-line loss calculation method for DC-DC MMC modulated by fundamental frequency modulation. Based on the characteristics of the modulation, the switching moments along with the instantaneous voltage and current can be calculated exactly, and the conduction loss and switching loss of each submodule can be expressed in a mathematical way. The calculation results are compared with the simulation results from a comprehensive switched model and show good accuracy performance within a relative error of ± 2% under different operating conditions.