The role of lipid metabolic status in tyrosine kinase inhibitors-treated patients with metastatic renal cell carcinoma is insufficient. To analyse the influence of dynamic changes of lipid metabolism on survival outcomes in tyrosine kinase inhibitors-treated metastatic renal cell carcinoma. Serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol were collected, both before tyrosine kinase inhibitors therapy and at different time points of tyrosine kinase inhibitors treatment duration. Other clinicopathological and survival data were retrospectively reviewed. The clinical outcomes, including tumour response, progression-free survival and overall survival, were analysed. Kaplan-Meier survival curves were plotted and the log-rank test was used to analyse statistical significance. A total of 127 patients with metastatic renal cell carcinoma, initially treated with tyrosine kinase inhibitors as first-line systemic therapy, were included. In the whole cohort, the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol fluctuated but gradually increased during tyrosine kinase inhibitors treatment. In survival analysis, the higher serum level of lipid metabolism, the longer progression-free survival was observed. In terms of overall survival, all post-treatment lipid metabolism, including the percentages of increasing change, were correlated with better survival. Further multivariate analysis showed that patients with five components of treatment-related dysfunction of lipid metabolism had superior survival to those with less than five components. However, lipid metabolism was not correlated with tumour response. Increasing parameters of lipid metabolism indicated improvement of survival in tyrosine kinase inhibitors-treated metastatic renal cell carcinoma, especially the increasing percentages. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.