Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease in which monocytes/macrophages infiltration and skewed T helper type (Th) 1 and Th17 cell responses participate in the development of the disease. Human peripheral blood monocytes are heterogeneous and can be divided into classical CD14(high)CD16(-), intermediate CD14(high)CD16(+), and nonclassical CD14(low)CD16(+) monocyte subsets. Compared to classical monocytes, CD16(+) monocytes are generally termed pro-inflammatory monocytes and play an important pathogenic role in autoimmune diseases. However, little is known about the immunophenotype and immunopathogenic role of peripheral blood CD16(+) monocytes in PBC. Thus, we investigated the phenotype and function of these circulating monocyte subsets from PBC patients. The frequencies of circulating CD14(high)CD16(+) and CD14(low)CD16(+) subpopulation were increased in disease compared with healthy controls. Among them, CD14(low)CD16(+) monocyte subset positively correlated with disease progress, liver damage indicators and serum C-reactive protein, respectively. Furthermore, the frequencies of Th1 and Th17 cells were upregulated and CD14(low)CD16(+) monocyte subset was also positively associated with Th1 cell frequency in PBC. Using a vitro coculture model, we further found that CD14(low)CD16(+) monocytes promoted Th1 cell polarization compared to classical monocytes. Interleukin-12 (IL-12) and direct contact of patient CD4(+)T cell and CD14(low)CD16(+) monocytes, were responsible for CD14(low)CD16(+) monocytes promotion of Th1 cells polarization in PBC. Our study demonstrated that the enhanced CD14(low)CD16(+) monocyte subset participated in fostering liver damage and inflammatory responses, and promoted Th1 cells skewing in PBC.