The Golgi apparatus and its resident proteins are utilized and regulated by viruses to facilitate their proliferation. Inthis study, we investigated Classical swine fever virus (CSFV) proliferation when the function of the Golgi wasdisturbed. Golgi function was disturbed using chemical inhibitors, namely, brefeldin A (BFA) and golgicide A (GCA),and RNA interfering targets, such as the Golgi-specific BFA-resistance guanine nucleotide exchange factor 1 (GBF1)and Rab2 GTPases. CSFV proliferation was significantly inhibited during RNA replication and viral particlegeneration after BFA and GCA treatment. CSFV multiplication dynamics were retarded in cells transfected withGBF1 and Rab2 shRNA. Furthermore, CSFV proliferation was promoted by GBF1 and Rab2 overexpression using alentiviral system. Hence, Golgi function is important for CSFV multiplication, and GBF1 and Rab2 participate inCSFV proliferation. Further studies must investigate Golgi-resident proteins to elucidate the mechanism underlyingCSFV replication.