Background: Pyrotinib maleate is a small molecule, irreversible inhibitor of HER1, HER2 and HER4 tyrosine kinases developed in China. A number of clinical studies have confirmed the good efficacy in treating patients with HER2-positive solid tumours and HER2-positive breast cancer brain metastases. In this study, we ulteriorly explore the curative effect and safety of pyrotinib in HER2-positive solid tumours brain metastases treatment. Methods: Clinical data from 53 patients with HER2-positive solid tumor brain metastases enrolled were compiled and analyzed. The impact of whether pyrrolizidine was combined with chemotherapy, a large molecule TKI, and intracranial local radiotherapy on PFS and intracranial PFS in the enrolled patients is somewhat outlined. Results: From June 2021 to December 2022, according to 53 patients with HER2-positive solid tumor brain metastases availably measured intracranial metastases meeting RECIST 1.1 criteria at baseline, with the dosing regimen based on pyrotinib and the combination or intracranial radiation therapy following the clinician's choice. The recorded patients included 49 patients with breast cancer, 2 patients with lung adenocarcinoma, and 1 patient with gastric cancer. A total of 37 patients were HER2-positive by immunohistochemistry, 4 patients were HER-positive by genetic testing, 9 patients were HER2-positive by fluorescence in situ hybridization, and the remaining 3 patients had unknown HER2 status. A total of 27 patients had one or more radiation treatments for intracranial metastases, 39 patients with treatment regimens combining chemotherapy with pyrotinib, and 19 patients with combination of large molecule TKI. The selected 53 patients base in the study, had disease progression due to new intracranial metastases or enlarged intracranial metastases in 42. The mPFS was 12 months for all patients and 13 months for intracranial metastases. Further collated analysis has shown there was no significant difference in mPFS between subgroups according to age, method of HER2 detection, lines of therapy, whether or not combined with chemotherapy, and possibility of combining with large molecule TKI therapy. There was a remarkable difference in PFS between the combined intracranial radiation therapy group and the non-combined intracranial radiation therapy group (14.6 months vs. 11.4 months, p = 0.042). There was also a significant variance in intracranial PFS between the combined intracranial radiation treatment group and the non-combined intracranial radiation treatment group (15.8 months vs. 12.0 months, p = 0.023). Conclusions: Pivotally, pyrotinib has shown good clinical efficacy in patients with HER2-positive solid tumor brain metastases. The results of this study suggest that early intervention with intracranial local radiation therapy is utterly essential for HER2-positive patients with brain metastases at baseline.