Objective: To investigate the immunoinflammatory response in the crosstalk of human oral keratinocytes (HOKs) with selected periodontal commensals and pathogens. Methods: Four representative viable oral bacteria, including periodontal commensals (Streptococcus mutans, Sm; and Actinomyces israelii, Ai) and pathogens (Aggregatibacter actinomycetemcomitans, Aa; and Porphyromonas gingivalis, Pg), were selected. A viable bacteria-HOKs interactive model was tested under various conditions of oxygen, antibiotics, duration and multiplicity of infection (MOI). The expression of IL-6 and IL-8 in HOKs was assessed by real-time qPCR and ELISA. Results: An MOI of 1 was determined to be the appropriate ratio of bacteria and HOKs with substantial amounts of viable bacterial cells and HOKs in an antibiotic-free medium under aerobic conditions for 2 h. Sm and Pg significantly upregulated the expression of IL-6 and IL-8 (P 0.05), while Ai and Aa could not induce significant levels of these cytokines with reference to the control. Conclusion: Within the limitations of this study, the current findings suggest that periodontal commensals and pathogens may differentially modulate immunoinflammatory response in human oral keratinocytes. Keywords: commensals, periodontopathogens, human oral keratinocytes, bacteria-host interaction, cytokines