To assess the effect of hydroxypropyl methylcellulose (HPMC) 2% to prevent dry eye during phacoemulsification in senile and diabetic patients. This prospective interventional case series comprised 60 eyes (44 patients) with age-related cataract scheduled for standardized phacoemulsification surgery. The patients were assigned to receive either balanced saline solution (BSS, 30 eyes) or HPMC 2% (30 eyes) during surgery. Preoperative and postoperative examinations (1, 3, 7 and 30 days) included measurements of automatic noninvasive tear film breakup time (NITBUT), fluorescein staining, Schirmer I test, tear meniscus height, depth and area and subjective symptoms. Intraoperative application frequency was also assessed. The mean age of patients was 68.7 ± 2.3 years. The application frequency of BSS during surgery was significantly reduced in HPMC group (P = 0.001). The incidence of dry eye syndrome (DES) was significantly reduced in HPMC group in both senile and diabetic patients. Scores of subjective symptoms were significantly higher in the BSS group in 1 day (P = 0.003) and 3 days (P = 0.043) postoperatively. The first and average NITBUT were significantly higher in HPMC group in 1 day and 3 days after surgery, respectively (P = 0.012 and P = 0.024, respectively). NITBUT values did not significantly change postoperatively in the HPMC group (P > 0.05), while they were significantly lower postoperatively in the BSS group. Application of HPMC 2% during phacoemulsification reduced the incidence of DES and improved patients’ satisfaction in both senile and diabetic cataract patients. It was also effective in maintaining corneal hydration and was able to significantly reduce the application frequency intraoperatively.