Piliostigma reticulatum is a species with high socio-economic potential. Unfortunately, in Burkina Faso, under the combined effect of climatic factors and anthropic actions, the species is experiencing a degradation compromising its survival. The present study was undertaken in order to contribute to promote its domestication by determining better conditions for seed germination and the determination of the substrate (organic or mineral) that allows a stronger, faster and homogeneous germination of seeds. Thus, the germination of P. reticulatum seeds was tested on ten (10) types of substrates. Also, the effect of substrate on seed germination and growth parameters was studied. The results revealed that germination is influenced by the type of substrate used. The best substrate for seed germination of Piliostigma reticulatum was a mixture of forest soil, Guiera senegalensis leaf compost and Burkina phosphate with a germination rate of 34.44%. The best growth of P. reticulatum seedlings is obtained with the substrates of Guiera senegalensis compost + forest soil + Burkina phosphate 13g and Guiera senegalensis compost + forest soil presents the greatest size with respective heights of 8.9 cm and 7.8 cm at day 30 after sowing. The results of the present study suggest avenues for further study with a view to sustainable management of the species.