Hannetjie de Clerq's career started at the age of 18 when she exhibited for the first time. Her work is unique in the South African art sphere and shows a juxtaposition of emotions, of things ancient and modern, strongly sensual, sometimes light-headed and often tinged with a sense of sadness. Her fascination for the purity of medieval iconography, interconnected with 20th century technology, social realities and the ambiguity of surrealism is obvious. The preferred media that she works in is tempera and oil on canvas. The inspiration for the special technique she uses in painting comes from frescoes and icons from the Middle Ages, especially Giotto's work. She feels that an over-explanation of her work renders it impotent and therefore does not title her paintings. For her, the beauty of art is in the interaction between the viewers with their subjective personal view of a specific painting, allowing specific meaning to be found in the imagery.
Hannetjie de Clerq has been acknowledged as one of South Africa's top artists by SASOL, resulting in her work forming part of the impressive SASOL art collection. She shares this honor with iconic South African artists like Walter Battis, Maggie Loubser, J.H Pierneef, Alexander Rose-Innes and Irma Stern.