Milk thistle Silybum marianum (L.) Gaertn. is one of the most researched medicinal plants, but at the same time it belongs to crops with wide industry potential whose growth requirements for marginal agroecological conditions or the response to agronomic interventions has not yet been sufficiently studied. The aim of the present research was to verify the effect of mineral nutrition (NPK 200 kg/ha) and humic acids applied to the soil (HUMAC Agro 250 kg/ha) on the main biometric parameters and the intensity of photosynthesis of milk thistle grown under less favourable climatic conditions of the semi-cold and humid foothills in Central Europe. The highest seed yield was achieved with the NPK variant in terms of dry matter 0.534 t/ha, in the HUMAC Agro variant 0.254 t/ha and with the untreated control 0.087 t/ha. The soil before the trial establishment was characterised by low nutrient content. The use of mineral fertiliser on NPK treatment eliminated the influence of low PK nutrients content of the soil, influencing the crop growth and yield/quality, while no doses of NPK were used on the HUMAC Agro variant and the untreated control. For both of the two sequences created (temperature and light), the highest photosynthesis rate was measured on untreated control (20.115 and 12.386 mmol/m2/s1), markedly lower on HUMAC Agro (16.386 and 9.653 mmol/m2/s1) – and the lowest on the NPK (10.933 and 7.813 mmol/m2/s1, respectively), in inverse proportion to the crop yield. Therefore, the size of the leaf area of the crop was decisive for the increased crop yield. The polynomial trend line of the photosynthesis rate according to the temperature sequence shows the photosynthesis rate and the torrential decrease by temperature increasing on untreated control compared with both treated variants. Both of these threats, mineral nutrition and use of humic preparations to soil, although they reduce the photosynthesis rate, have a wide range of complex effects that provide an opportunity to optimise the growth and yield of milk thistle. Ideally, the mineral nutrition and humic preparations should be used in combination with the crop of milk thistle for medicinal and energy purposes.