Hepatitis B virus (HBV) hijacks host proteins to manipulate cellular physiology and metabolism, facilitating its replication. Transgelin 2 (TAGLN2) ，an actin-binding protein, is highly expressed in HBV-associated hepatocellular carcinoma, yet its role in viral infection remains unclear. I Here, we demonstrated that HBV upregulated TAGLN expression in vitro and in vivo. TAGLN depletion impaired HBV replication and transcription while promoted mitochondrial fission and enhanced ATP production. Through mitochondrial proteomics, we identified Optic Atrophy 1 (OPA1)，a key dynamin governing mitochondrial fusion, as a downstream effector. Silencing OPA1 downregulated TAGLN and suppressed HBV replication, whereas OPA1 overexpression exerted the opposite effects. Mechanistically, TAGLN and OPA1 form a reciprocal regulatory axis to sustain HBV propagation. Our study unveils a novel TAGLN-OPA1 axis critical for HBV replication, providing insights into host-directed antiviral strategies.