The paper illustrates a case study of fluid selection for an internal combustion engine heat recovery organic Rankine cycle (ORC) system having the net power of about 30 kW. Various criteria of fluid selection are discussed. Particular attention is paid to thermodynamic performance of the system and human safety. The selection of working fluid for the ORC system has a large impact on the next steps of the design process, i.e., the working substance affects the turbine design and the size and type of heat exchangers. The final choice is usually a compromise between thermodynamic performance, safety and impact on natural environment. The most important parameters in thermodynamic analysis include calculations of net generated power and ORC cycle efficiency. Some level of toxicity and flammability can be accepted only if the leakages are very low. The fluid thermal stability level has to be taken into account too. The economy is a key aspect from the commercial point of view and that includes not only the fluid cost but also other costs which are the consequence of particular fluid selection. The paper discusses various configurations of the ORC system – with and without a regenerator and with direct or indirect evaporation. The selected working fluids for the considered particular power plant include toluene, DMC (dimethyl carbonate) and MM (hexamethyldisiloxane). Their advantages and disadvantages are outlined.