Objective: This study aims to explore the differences in perinatal depression stigma between South China and Northwest China and analyze its influencing factors, so as to provide a basis for formulating targeted intervention strategies. Design: A qualitative research design was adopted. Setting: The study was conducted in two hospitals in Guangdong Province (South China) and two hospitals in Gansu Province (Northwest China). Population: 18 perinatal women, including 9 from South China and 9 from Northwest China, who met the inclusion criteria (EPDS score ≥9, depression stigma scale score ≥36, and normal language communication ability). Methods: Semi-structured in-depth interviews were conducted, and the data were analyzed using NVivo 14 software based on Colaizzi’s seven-step analysis method. Main Outcome Measures: Differences in perinatal depression stigma between the two regions and influencing factors at individual, family, and social levels. Results: South China had lower stigma due to developed economy, open information, and inclusive concepts, while Northwest China had higher stigma due to limited knowledge popularization and traditional concepts. Influencing factors included cognitive level, religious culture, family support, regional economy, and social medical conditions. Conclusions: There are significant regional differences in perinatal depression stigma in China, affected by multiple factors. It is necessary to strengthen regional targeted interventions, improve social support systems, and promote scientific knowledge popularization to reduce stigma and improve help-seeking behavior.