Ethanol is a key factor in the pathogenesis of alcoholic liver disease (ALD), commonly characterized as liver inflammation. Recently, circular (circ)RNAs have emerged as important targets to cure liver diseases. However, there are no studies investigating the role of circ_1639 in reducing inflammatory responses in ALD. In this study, we found that circ_1639 was upregulated in Kupffer cells from the livers of alcohol fed mice. We hypothesized that circ_1639 inhibition is a potential novel therapy for treating ALD. To test this hypothesis, RAW 264.7 cells were treated with ethanol and transfected with circ_1639 overexpression or knockdown plasmids. We present western blotting, qRT-PCR, and ELISA data that suggest that circ_1639 is a proinflammatory factor in the liver and is involved in the activation of the NF-κB signaling pathway. Using luciferase reporter assay, we confirmed that microRNA (miR)-122 is a target gene of circ_1639. We also show that TNFRSF13C is a key regulator of RAW 264.7 cell activation, and acts as a downstream target for miR-122. In summary, our results suggest that inhibition of circ_1639 expression may reduce inflammatory responses in ALD.