Metal ion homeostasis and heavy metal detoxification systems are regulated by certain genes associated with metal ion transport. Metallothionein (MT) and metal response element binding transcription factor 1 (MTF‑1) are important regulatory proteins involved in the mediation of intracellular metal ion balance. Differences in the zinc‑binding affinities of the zinc fingers of MTF‑1 and the α‑ and β‑domains of MT facilitate their regulation of Zn2+ concentration. Alterations in the intracellular concentration of Zn2+ influence the MTF‑1 zinc finger number, and MTF‑1 containing certain zinc finger numbers regulates the expression of corresponding target genes. The present review evaluates the association between zinc finger number in MTF‑1 protein, MTF‑1 target genes and the mechanism underlying MT regulation of the zinc finger number in MTF‑1.