Aim: The current management of advanced gastric or gastro-oesophageal junction adenocarcinoma remains unsatisfactory. We investigated the efficacy and safety of the combination therapy of apatinib and S-1, considering the potential advantage of home-based treatment without hospital admission, in patients with platinum-refractory gastric or gastro-oesophageal junction adenocarcinoma. Methods：Between April 2015 and May 2019, we included 37 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma refractory to first-line platinum-containing therapy, who were treated with apatinib at an initial dose of 500 mg once daily continuously and S-1 at a dose of 40-60 mg twice daily on days 1-14 of a 21-day cycle. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rates, disease control rates, and safety. Results：At the data cutoff, the median PFS and OS were 4.2 months and 8.2 months, respectively. Of 37 eligible patients, 8 (21.6%) patients reached objective responses, 31 (83.8%) patients reached disease control. Grade 3 or 4 adverse events occurred in 8 (21.6%) patients, including hand-foot syndrome, hypertension, and diarrhea, etc. Conclusions: The combination of Apatinib and S-1 showed promising efficacy and manageable toxicity as a home-based, second-line therapy in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma refractory to platinum-containing therapy.