Introduction: The homeodomain-interacting protein kinase (HIPK) family consists of four evolutionarily conserved and highly related nuclear serine/threonine kinases of recent discovery. They interact with homeobox proteins and other transcription factors, as well as transcriptional coactivators or corepressors depending on the cellular context. HIPK proteins are sensors for various extracellular stimuli, which control key cellular functions such as signal transduction to downstream effectors that regulate apoptosis, embryonic development, DNA-damage response, and cellular proliferation. Thus, HIPKs are involved in proliferative diseases such as cancer and fibrosis. mRNA levels and protein stability tightly regulate expression levels of HIPKs. Methods: Here, we review recent works investigating the regulation of HIPKs expression by microRNAs (miRNAs) that are involved in the control of cell proliferation, sensitivity to chemotherapeutic drugs, epithelial-mesenchymal transition, and glucose-stimulated insulin secretion. Conclusion: It appears that HIPK family members, and their related miRNAs, may be considered as novel therapeutic targets for treating cancer, renal fibrosis and type 2 diabetes.