Autophagy is a highly conserved mechanism to overcome various stresses and recycle cytoplasmic components and organelles. Ubiquitin-like (UBL) protein Atg12 is a key protein involved in autophagosome formation through stimulation of Atg8 conjugation to phosphatidylethanolamine. Here, we describe the identification of the autophagy-related gene Acatg12, encoding an Atg12 homologous protein in the cephalosporin C producing fungus Acremonium chrysogenum. Disruption of Acatg12 impaired the delivery and degradation of eGFP-Atg8, indicating that the autophagic process was blocked. Meanwhile, conidiation was dramatically reduced in the Acatg12 disruption mutant (Delta Acatg12). In contrast, cephalosporin C production was increased twofold in Delta Acatg12, but fungal growth was reduced after 6 days fermentation. Consistent with these results, the transcriptional level of the cephalosporin biosynthetic genes was increased in Delta Acatg12. The results extend our understanding of autophagy in filamentous fungi.