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BACKGROUND:?A? better? understanding? of? the? molecular?mechanisms?in?liver?regeneration?holds?promise?for?exploring?the?new?potential?therapy?for?liver?failure.?The?present?study?was?to?investigate?the?role?of?zinc?ifnger?and?BTB?domain-containing?protein?20?(ZBTB20),?a?potential?factor?associated?with?liver?regeneration,?in?a?model?of?70%?hepatectomy?in?mice. METHODS:?Parameters?for?liver?proliferation?such?as?liver/body?ratio?and?BrdU?positivity?were?obtained?via?direct?measurement?and? immunohistochemistry.? The? levels? of? zinc? ifngers? and?homeoboxes?2?(ZHX2),?ZBTB20,?alpha-fetoprotein?(AFP)?and?glypican?3?(GPC3)?transcripts?in?the?regenerating?liver?tissue?of?a?70%?hepatectomy?rodent?model?were?monitored?by?real-time?PCR?analysis?at?different?time?points.?Knockdown?of?ZBTB20?was?performed?to?characterize?its?regulatory?function. RESULTS:?A?negatively?regulating?relationship?between?ZHX2,?ZBTB20?and?AFP,?GPC3?was?revealed?from?24?to?72?hours?after?70%?hepatectomy.?ZBTB20?appears?to?negatively?regulate?AFP?and?GPC3?transcription?since?the?knockdown?of?ZBTB20?promoted?the?proliferation?of?hepatocytes?and?the?expression?of?AFP?and?GPC3. CONCLUSION:?In?addition?to?AFP,?GPC3?and?ZHX2,?ZBTB20?is?a?new?regulator?in?liver?regeneration?and?the?decrease?of?ZBTB20?expression?following?70%?hepatectomy?promotes?AFP?and?GPC3?expression.