It is known that the day-night shift-rotation has a negative impact on the immune system. The underlying mechanism remains to be further investigated. Probiotics have regulatory effects on immune functions. This study aims to investigate the role of probiotic ingestion in preventing the DEC205+ dendritic cell (decDC) dysfunction in day-night shift-engaging nurses. In this study, blood samples were collected from day-night shift-rotating nurses who took or did not take yogurt (containing C. Butyricum) during the night shift (NS). decDC functions were evaluated with pertinent immunological approaches. We observed that the immune tolerogenic functions and interleukin (IL)-10 expression were impaired in decDCs of nurses after NS. HDAC11 was detected in decDCs that was markedly up regulated after NS. The HDAC11 levels were negatively correlated with the immune tolerogenic functions in decDCs. Ingestion of probiotic-containing yogurt during NS efficiently suppressed Bmal1 and HDAC11 levels as well as up regulated the immune regulatory functions in decDCs. In conclusion, NS has a negative impact on decDC immune tolerogenic functions, which can be prevented by ingesting probiotics-containing yogurt during NS.