Objective To analyze the differences in serum lipid levels and clinical symptoms among hospitalized elderly depressive dissorder patients of different genders who were at risk of suicide during the acute phase. Methods This study was a cross-sectional study. From July 2021 to December 2022， 143 elderly inpatients with acute depressive dissorder at risk of suicide at Beijing Anding Hospital， Capital Medical University were selected as the study subject， with 63 males and 80 females. This study collected general information and compared the anxiety and depression of patients of different genders using the Hamilton Anxiety Rating Scale （HAMA） and the 24-item Hamilton Depression Rating Scale （HAMD-24）. This study compared the levels of serum adrenocorticotropic hormone （ACTH）， cortisol， total thyroxine （TT4 ）， total triiodothyronine （TT3 ）， free triiodothyronine （FT3 ）， free thyroxine （FT4 ）， thyroid stimulating hormone （TSH）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in patients of different genders. Spearman correlation was used to analyze the correlation between serum lipid levels and HAMD-24 and HAMA scores in patients of different genders. Results The proportion of divorced/ widowed female patients was higher than that of male patients ［32.50% （26/80） vs 7.94% （5/63）］， and the difference was statistically significant （χ2 =12.525， P＜0.001）. The weight loss factor score ［0 （0， 2.00） vs 0 （0， 1.00）］， total HAMD-24 score ［31.00 （28.00， 36.00） vs 28.00 （25.25， 33.75）］， somatic anxiety factor score ［8.00 （6.00， 11.00） vs 6.00 （4.00， 8.00）］， and total HAMA score ［23.00 （20.00， 27.00） vs 21.00 （19.00， 25.00）］ of male patients were higher than those of female patients， and the differences were statistically significant （all P＜ 0.05）. The levels of TC ［（4.30±1.05） vs （4.97±0.96） mmol/L］， HDL-C ［（1.18±0.30） vs （1.29±0.28） mmol/L］， LDC-C ［（2.70±0.81） vs （3.16±0.75） mmol/L］， and TG ［1.09 （0.87， 1.46） vs 1.45 （1.09， 2.02） mmol/L］ in male patients were lower than those in female patients， and the differences were statistically significant （all P＜ 0.05）. Correlation analysis showed that the levels of TC， LDL-C， TG in male patients were negatively correlated with the despair factor score in HAMD， and the differences were statistically significant （r=-0.280， -0.341， -0.312； P＜ 0.05）. There was no correlation between the levels of serum lipid and HAMD and HAMA scores in female patients （all P＞ 0.05）. Conclusions Compared with female patients， male elderly patients with acute depression at risk of suicide have more severe clinical symptoms and lower serum lipid levels， and serum lipid levels are negatively correlated with clinical symptoms.