In this study, we aimed to investigate the acid tolerance response (ATR) and the formation pattern of crossprotection in acid-adapted and non-adapted strains during the production of fermented sausage. Listeria innocua was selected as a surrogate for L. monocytogenes. It was induced in an acidic environment (pH 5.4) for 18 hours, yielding an acid-adapted strain. The survival counts of acid-adapted and non-adapted L. innocua during sausage fermentation and the changes in acid, heat and osmotic resistance were determined. The results indicated that the counts of the acid-adapted and non-adapted strains decreased by 1.33 (lg(CFU/g)) and 1.06 (lg(CFU/g)), respectively, at the end of sausage production, the decrease in the former being significantly smaller than that in the latter (P < 0.05). Moreover, the D values of the acid-adapted strain under acidic, thermal and hypertonic conditions during the fermentation process were significantly higher than those of the non-adapted strain (P < 0.05). This suggests that the acid stress in raw meat could significantly enhance the survival of L. innocua during the production of fermented sausage and significantly improve its acid, heat and osmotic resistance. The acid, heat and osmotic resistance of the non-adapted strain significantly increased during the production of fermented sausage (P < 0.05), indicating that ATR occurred in L. innocua during the sausage production process, triggering cross-protection against heat and osmosis. Although both acid-adapted and non-adapted L. innocua were significantly inhibited during sausage production, there were still a large number of residues at the end of the production process (the number of colonies declined < 5 (lg(CFU/g)) during the production process), and the acid, heat and osmotic resistance significantly increased during the production process. These results suggest that the potential risk of ATR in pathogenic bacteria should be fully considered in the improvement of the fermentation process.