Background: Several studies in solid tumors have shown that the excision repair cross-complementation group 1 (ERCC1) and class III β-tubulin (TUBB3) expressions can predict response to chemoradiotherapy treatments and could be considered as prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients (pts) treated with different neoadjuvant therapeutic schedules. Methods: ERCC1 and TUBB3 were detected in 88 pts with LACSCC by immunohistochemical analysis. Sixty-two pts were included in three different prospective phase II trials in the neoadjuvant setting carried out by GOCS and grouped as follows: vinorelbine or docetaxel (Group A, n=44), and ifosfamide-vinorelbine-cisplatin (Group B, n=18). Both groups were compared with standard cisplatin chemoradiotherapy (Group C, n=26). Clinical data at baseline, disease free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors. Results: The median age was 43.5 years (range: 27-74). Thirty-five (39.8%) and 18 (20.5%) of 88 pts were classified as high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p =.034) and progressive disease (49% vs. 28%). Poor DFS (p =.021) and OS (p =.005) were observed in Group C pts whose tumors had high ERCC1 expression. No differences were observed either in Group A or B between the studied variables. Multivariate analysis for the whole series showed that ERCC1 expression, FIGO stage and pre-treatment hemoglobin level were significant prognostic factors (p =.002, p =.008 and p =.005, respectively). Conclusions: Our study confirms that ERCC1 expression could be a predictive and prognostic factor in LACSCC patients that received cisplatin monotherapy. Conversely, TUBB3 status had no impact on survival in patients treated with antimicrotubule agents.