The low capability of self-repair in hyaline cartilage tissue and chondrocytes de-differentiating when grown in vitro (e.g., for tissue engineering approaches) limits articular cartilage repair. It has been shown that the embryonic architectural transcription factors of the high-mobility-group-A (HMGA) protein family affect the regulation of cell differentiation by influencing the state of cell chromatin and are involved in hyaline cartilage development by affecting the expression of chondrocyte-specific marker genes. Thus, the control of cartilage cell proliferation and differentiation by HMGA proteins promises to be an important aspect in cartilage tissue repair. To elucidate the effects on the proliferative activity of hyaline chondrocytes, HMGA proteins were recombinantly expressed, highly purified, and applied to porcine hyaline cartilage cells growing in in vitro monolayer cell culture. Direct application of HMGA1a, HMGA1b, and HMGA2 proteins onto porcine chondrocytes was shown to have a highly significant influence on cell proliferation. Greater proliferation of chondrocytes was achieved than in the untreated control group, indicating a promising approach to enhancing cartilage tissue repair.