Objective To investigate the correlation between the changes of serum heat shock protein 60 (HSP60), fibronectin-3 (Ficolin-3), thrombin-activated fibrinolysis inhibitor (TAFI) levels and the therapeutic effect in elderly patients with chronic glomerulonephritis (CGN), and to analyze its evaluation value for the therapeutic effect. Methods A total of 112 elderly patients with CGN diagnosed and treated in our hospital from January 2023 to January 2025 were prospectively selected as the study group, and 112 healthy subjects were selected as the control group. The levels of serum HSP60, Ficolin-3 and TAFI were compared between the two groups. The study group was treated with conventional western medicine for 3 months. According to the treatment effect, it was divided into effective subgroup (74 cases) and ineffective subgroup (38 cases). The levels of serum HSP60, Ficolin-3 and TAFI were compared, the influencing factors of treatment effect were analyzed, and the evaluation value of serum HSP60, Ficolin-3 and TAFI on treatment effect was analyzed. Results The levels of serum HSP60, Ficolin-3 and TAFI in the study group were higher than those in the control group (P<0.05). The levels of serum HSP60, Ficolin-3 and TAFI in ineffective subgroup after 1 month and 3 months of treatment were higher than those in effective subgroup (P<0.05). The levels of serum HSP60, Ficolin-3 and TAFI after 1 month of treatment were independent influencing factors of therapeutic effect (P<0.05). After 1 month of treatment, the AUC values of serum HSP60, Ficolin-3, TAFI alone and combined evaluation of therapeutic effect were 0.757, 0.739, 0.767, 0.881, respectively, and the AUC value of combined evaluation was significantly higher than that of single index (P<0.05). Conclusion The increase of serum HSP60, Ficolin-3 and TAFI levels in elderly CGN patients is an independent influencing factor for the therapeutic effect. The detection of their levels has certain evaluation value for the therapeutic effect, and the evaluation value of combined detection of their levels is higher.